Editing Amide

{{short description|1=Organic compounds of the form RC(=O)NR′R″}}
{{about|organic amides with the formula {{chem2|RC(\dO)NR′R″}}|the anion {{chem2|NH2-}}|Azanide|other uses|Amide (functional group)}}
{{Distinguish|imide}}
{{Use dmy dates|date=July 2020}}
[[File:Amide-(tertiary).svg|thumb|right|General structure of an amide (specifically, a carboxamide)]]
[[File:Formamide-3D-balls.png|thumb|right|[[Formamide]], the simplest amide]]
[[File:Asparagine w functional group highlighted.png|thumb|right|[[Asparagine]] ([[zwitterionic]] form), an [[amino acid]] with a side chain (highlighted) containing an amide group]]

In [[organic chemistry]], an '''amide''',<ref>{{cite web|url=http://www.collinsdictionary.com/dictionary/english/amide|title=Amide definition and meaning - Collins English Dictionary|author=|date=|website=www.collinsdictionary.com|accessdate=15 April 2018}}</ref><ref>{{Cite American Heritage Dictionary|amide}}</ref><ref>{{cite web|url=http://www.oxforddictionaries.com/us/definition/english/amide|archive-url=https://web.archive.org/web/20150402184403/http://www.oxforddictionaries.com/us/definition/english/amide|url-status=dead|archive-date=2 April 2015|title=amide - Definition of amide in English by Oxford Dictionaries|author=|date=|website=Oxford Dictionaries – English|accessdate=15 April 2018}}</ref> also known as an '''organic amide''' or a '''carboxamide''', is a [[chemical compound|compound]] with the general formula {{chem2|R\sC(\dO)\sNR′R″}}, where R, R', and R″ represent any group, typically [[organyl]] [[functional group|groups]] or [[hydrogen]] atoms.<ref>{{goldbookref|file=A00266|title=amides}}</ref><ref name=Fletcher>{{cite book | first = John H. |last = Fletcher | chapter = Chapter 21: Amides and Imides | title = Nomenclature of Organic Compounds: Principles and Practice | pages = 166–173 | doi = 10.1021/ba-1974-0126.ch021 | volume = 126 | isbn = 9780841201910 | chapter-url = https://archive.org/details/nomenclatureofor0000flet/page/166 | location = Washington, DC | publisher = [[American Chemical Society]] | year = 1974 }}</ref> The amide group is called a [[peptide bond]] when it is part of the [[Polymer backbone|main chain]] of a [[protein]], and an [[isopeptide bond]] when it occurs in a [[side chain]], as in [[asparagine]] and [[glutamine]]. It can be viewed as a [[Derivative (chemistry)|derivative]] of a [[carboxylic acid]] ({{chem2|R\sC(\dO)\sOH}}) with the [[hydroxyl]] group ({{chem2|\sOH}}) replaced by an [[amino]] group ({{chem2|\sNR′R″}}); or, equivalently, an [[acyl group|acyl (alkanoyl) group]] ({{chem2|R\sC(\dO)\s}}) joined to an amino group.

Common of amides are [[formamide]] ({{chem2|H\sC(\dO)\sNH2}}), [[acetamide]] ({{chem2|H3C\sC(\dO)\sNH2}}), [[benzamide]] ({{chem2|C6H5\sC(\dO)\sNH2}}), and [[dimethylformamide]] ({{chem2|H\sC(\dO)\sN(\sCH3)2}}). Some uncommon examples of amides are ''N''-chloroacetamide ({{chem2|H3C\sC(\dO)\sNH\sCl}}) and chloroformamide ({{chem2|Cl\sC(\dO)\sNH2}}).

Amides are qualified as [[primary (chemistry)|primary]], [[secondary (chemistry)|secondary]], and [[tertiary (chemistry)|tertiary]] according to the number of acyl groups bounded to the nitrogen atom.<ref name=Fletcher /><ref>{{GoldBookRef|title=Amides|file=A00266}}</ref>

==Nomenclature==
{{Main|IUPAC nomenclature of organic chemistry#Amines and amides}}
The core {{chem2|\sC(\dO)\s(N)}} of amides is called the '''amide group''' (specifically, '''carboxamide group''').

In the usual nomenclature, one adds the term "amide" to the stem of the parent acid's name. For instance, the amide derived from [[acetic acid]] is named [[acetamide]] (CH<sub>3</sub>CONH<sub>2</sub>). IUPAC recommends [[ethanamide]], but this and related formal names are rarely encountered. When the amide is derived from a primary or secondary amine, the substituents on nitrogen are indicated first in the name. Thus, the amide formed from [[dimethylamine]] and [[acetic acid]] is ''N'',''N''-dimethylacetamide (CH<sub>3</sub>CONMe<sub>2</sub>, where Me = CH<sub>3</sub>). Usually even this name is simplified to [[dimethylacetamide]]. Cyclic amides are called [[lactam]]s; they are necessarily secondary or tertiary amides.<ref name=Fletcher /><ref>{{BlueBook2004|rec=66.1}} Full text (PDF) of Draft Rule P-66: [https://old.iupac.org/reports/provisional/abstract04/BB-prs310305/Chapter6-Sec66.pdf Amides, Imides, Hydrazides, Nitriles, Aldehydes, Their Chalcogen Analogues, and Derivatives]</ref>

==Applications==
{{See also|polyamide|peptide bond}}
Amides are pervasive in nature and technology. [[Protein]]s and important [[plastic]]s like [[nylon]]s, [[aramid]]s, [[Twaron]], and [[Kevlar]] are [[polymer]]s whose units are connected by amide groups ([[polyamide]]s); these linkages are easily formed, confer structural rigidity, and resist [[hydrolysis]]. Amides include many other important biological compounds, as well as many [[drug]]s like [[paracetamol]], [[penicillin]] and [[LSD]].<ref>{{Cite journal |doi=10.1016/j.jep.2012.05.038 |title=Alkamid database: Chemistry, occurrence and functionality of plant ''N''-alkylamides |year=2012 |last1=Boonen |first1=Jente |last2=Bronselaer |first2=Antoon |last3=Nielandt |first3=Joachim |last4=Veryser |first4=Lieselotte |last5=De Tré |first5=Guy |last6=De Spiegeleer |first6=Bart |journal=Journal of Ethnopharmacology |volume=142 |issue=3 |pages=563–590 |pmid=22659196 |hdl=1854/LU-2133714 |url=https://biblio.ugent.be/publication/2133714/file/2140565.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://biblio.ugent.be/publication/2133714/file/2140565.pdf |archive-date=2022-10-09 |url-status=live |hdl-access=free}}</ref> Low-molecular-weight amides, such as dimethylformamide, are common solvents.

==Structure and bonding==
[[File:CSD CIF ACEMID06.jpg|thumb|288 px|Structure of acetamide [[hydrogen-bond]]ed dimer from [[X-ray crystallography]].  Selected distances: C-O: 1.243, C-N, 1.325, N---O, 2.925 Å. Color code: red = O, blue = N, gray = C, white = H.<ref>{{cite journal |doi=10.1107/S1600536803019494 |title=A new refinement of the orthorhombic polymorph of acetamide |date=2003 |last1=Bats |first1=Jan W. |last2=Haberecht |first2=Monika C. |last3=Wagner |first3=Matthias |journal=Acta Crystallographica Section E |volume=59 |issue=10 |pages=o1483–o1485 }}</ref>]]
The lone pair of [[electron]]s on the nitrogen atom is delocalized into the [[Carbonyl group]], thus forming a partial [[double bond]] between nitrogen and carbon. In fact the O, C and N atoms have [[molecular orbital]]s occupied by [[delocalized electron]]s, forming a [[conjugated system]]. Consequently, the three bonds of the nitrogen in amides is not pyramidal (as in the [[amine]]s) but planar. This planar restriction prevents rotations about the N linkage and thus has important consequences for the mechanical properties of bulk material of such molecules, and also for the configurational properties of macromolecules built by such bonds. The inability to rotate distinguishes amide groups from [[ester]] groups which allow rotation and thus create more flexible bulk material.

The C-C(O)NR<sub>2</sub> core of amides is planar.  The C=O distance is shorter than the C-N distance by almost 10%.  The structure of an amide can be described also as a [[resonance structure|resonance]] between two alternative structures: neutral (A) and [[zwitterionic]] (B).
:[[File:Amide resonance v2.svg|300px|thumb|none]]

It is estimated that for [[acetamide]], structure A makes a 62% contribution to the structure, while structure B makes a 28% contribution (these figures do not sum to 100% because there are additional less-important resonance forms that are not depicted above). There is also a hydrogen bond present between the hydrogen and nitrogen atoms in the active groups.<ref name = Kemnitz>{{Cite journal|doi=10.1021/ja0663024|title="Amide Resonance" Correlates with a Breadth of C−N Rotation Barriers|year=2007|last1=Kemnitz|first1=Carl R.|last2=Loewen|first2=Mark J.|journal=Journal of the American Chemical Society|volume=129|issue=9|pages=2521–8|pmid=17295481}}</ref> Resonance is largely prevented in the very strained [[quinuclidone]].
<!--needs:
barrier from DMF, and a more general ref than this JACS rpt
comment on syn and anti secondary amides-->

In their IR spectra, amides exhibit a moderately intense ''ν''<sub>CO</sub> band near 1650&nbsp;cm<sup>−1</sup>.  The energy of this band is about 60&nbsp;cm<sub>−1</sub> lower than for the ''ν''<sub>CO</sub> of esters and ketones.  This difference reflects the contribution of the zwitterionic resonance structure.

===Basicity===
Compared to [[amine]]s, amides are very weak [[base (chemistry)|base]]s. While the [[conjugate acid]] of an [[amine]] has a [[pKa|p''K''<sub>a</sub>]] of about 9.5, the [[conjugate acid]] of an amide has a p''K''<sub>a</sub> around −0.5. Therefore, compared to amines, amides do not have [[acid–base]] properties that are as noticeable in [[water]]. This relative lack of basicity is explained by the withdrawing of electrons from the amine by the carbonyl. On the other hand, amides are much stronger [[Base (chemistry)|base]]s than [[carboxylic acid]]s, [[ester]]s, [[aldehyde]]s, and [[ketone]]s (their conjugate acids' p''K''<sub>a</sub>s are between −6 and −10).

The proton of a primary or secondary amide does not dissociate readily; its p''K''<sub>a</sub> is usually well above 15. Conversely, under extremely acidic conditions, the carbonyl [[oxygen]] can become protonated with a p''K''<sub>a</sub> of roughly −1. It is not only because of the positive charge on the nitrogen but also because of the negative charge on the oxygen gained through resonance.

===Hydrogen bonding and solubility===
Because of the greater electronegativity of oxygen than nitrogen, 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. These hydrogen bonds also have an important role in the [[secondary structure]] of proteins.

The [[Solubility|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 [[Dimethylformamide|''N'',''N''-dimethylformamide]], exhibit low solubility in water.

==Reactions==
<!-- This section is linked from [[Organic reaction]] -->

Amides do not readily participate in nucleophilic substitution reactions. Amides are stable to water, and are roughly 100 times more stable towards [[hydrolysis]] than esters.{{citation needed|date=October 2024}} Amides can, however, be hydrolyzed to carboxylic acids in the presence of acid or base. The stability of [[peptide bond|amide bonds]] has biological implications, since the [[amino acid]]s that make up [[protein]]s are linked with amide bonds. Amide bonds are resistant enough to hydrolysis to maintain protein structure in [[aqueous]] environments but are susceptible to catalyzed hydrolysis.{{citation needed|date=October 2024}}

Primary and secondary amides do not react usefully with carbon nucleophiles. Instead, [[Grignard reagent]]s and organolithiums deprotonate an amide N-H bond. Tertiary amides do not experience this problem, and react with carbon nucleophiles to give [[ketone]]s; the [[sodium amide|amide]] anion (NR<sub>2</sub><sup>−</sup>) is a very strong base and thus a very poor leaving group, so nucleophilic attack only occurs once. When reacted with carbon nucleophiles, [[N,N-dimethylformamide|''N'',''N''-dimethylformamide]] (DMF) can be used to introduce a [[formyl]] group.<ref>{{cite book|title=Comprehensive Organic Functional Group Transformations|year=1995|publisher=Pergamon Press|location=Oxford|isbn=0080423248|edition=1st|editor1 = Alan R. Katritzky|editor-link = Alan R. Katritzky|editor2-last=Meth-Cohn|editor2-first=Otto|editor3 = Charles Rees|editor3-link = Charles Rees|page=[https://archive.org/details/comprehensiveorg0000unse/page/90 90]|volume=3|url=https://archive.org/details/comprehensiveorg0000unse/page/90}}</ref>

[[File:Formylation of Benzene using Phenyllithium and DMF.png|900px|Because tertiary amides only react once with organolithiums, they can be used to introduce aldehyde and ketone functionalities. Here, DMF serves as a source of the formyl group in the synthesis of benzaldehyde.|thumb|none]]

Here, [[phenyllithium]] '''1''' attacks the carbonyl group of DMF '''2''', giving tetrahedral intermediate '''3'''. Because the dimethylamide anion is a poor leaving group, the intermediate does not collapse and another nucleophilic addition does not occur. Upon acidic workup, the alkoxide is protonated to give '''4''', then the amine is protonated to give '''5'''. Elimination of a neutral molecule of [[dimethylamine]] and loss of a proton give benzaldehyde, '''6'''.

:[[File:Acid-CatAmideHydrolMarch.png|320 px|thumb|Mechanism for acid-mediated hydrolysis of an amide.<ref>{{March6th}}</ref>]]

===Hydrolysis===
Amides hydrolyse in hot [[alkali]] as well as in strong [[acid]]ic conditions. Acidic conditions yield the carboxylic acid and the ammonium ion while basic hydrolysis yield the carboxylate ion and ammonia. The protonation of the initially generated amine under acidic conditions and the deprotonation of the initially generated carboxylic acid under basic conditions render these processes non-catalytic and irreversible. Electrophiles other than protons react with the [[carbonyl]] oxygen. This step often precedes hydrolysis, which is catalyzed by both [[Brønsted acid]]s and [[Lewis acid]]s. [[Peptidase]] enzymes and some synthetic catalysts often operate by attachment of electrophiles to the carbonyl oxygen.

{| class="wikitable sortable"
!Reaction name !! Product !! class="unsortable" | Comment
|-
| Dehydration
|Nitrile
| Reagent: [[phosphorus pentoxide]]; [[benzenesulfonyl chloride]]; [[TFAA]]/[[pyridine|py]]<ref>{{US patent|5935953}}</ref>
|-
| [[Hofmann rearrangement]]
|Amine with one fewer carbon atom
|Reagents: [[bromine]] and [[sodium hydroxide]]
|-
| [[Amide reduction]]
| Amines, aldehydes
|Reagent: [[lithium aluminium hydride]] followed by hydrolysis
|-
|[[Vilsmeier–Haack reaction]]
|[[Aldehyde]] (via [[imine]])
| [[Phosphoryl chloride|{{chem2|POCl3}}]], aromatic substrate, formamide
|-
|[[Bischler–Napieralski reaction]]
|Cyclic aryl [[imine]]
| [[Phosphoryl chloride|{{chem2|POCl3}}]], [[thionyl chloride|{{chem2|SOCl2}}]], etc.
|-
|[[Darzens reaction|Tautomeric chlorination]]||[[Imidoyl chloride]]||[[Oxophilic]] halogenating agents, e.g. [[Phosgene|COCl<sub>2</sub>]] or [[Thionyl chloride|SOCl<sub>2</sub>]]
|}

==Synthesis==
<!-- This section is linked from [[Organic reaction]] -->

===From carboxylic acids and related compounds===
Amides are usually prepared by coupling a [[carboxylic acid]] with an [[amine]]. The direct reaction generally requires high temperatures to drive off the water:
:{{chem2|RCO2H + R'2NH → RCO2-  +  R'2NH2+}}
:{{chem2|RCO2-  +  R'2NH2+ → RC(O)NR'2 + H2O}}

[[Ester]]s are far superior{{explain|date=March 2025}} substrates relative to carboxylic acids.<ref>{{cite journal|last1=Corson|first1=B. B.|last2=Scott|first2=R. W.|last3=Vose|first3=C. E.|title=Cyanoacetamide|journal=Organic Syntheses|date=1941|volume=1|page=179|doi=10.15227/orgsyn.009.0036}}</ref><ref>{{cite journal|last1=Jacobs|first1=W. A.|title=Chloroacetamide|journal=Organic Syntheses|date=1941|volume=1|page=153|doi=10.15227/orgsyn.007.0016}}</ref><ref>{{cite journal|last1=Kleinberg|first1=J.|last2=Audrieth|first2=L. F.|title=Lactamide|journal=Organic Syntheses|date=1955|volume=3|page=516|doi=10.15227/orgsyn.021.0071}}</ref>{{better source needed|date=March 2025}}

Further "activating" both [[acid chloride]]s ([[Schotten-Baumann reaction]]) and [[anhydride]]s ([[Lumière–Barbier method]]) react with amines to give amides:
:{{chem2|RCO2R" + R'2NH → RC(O)NR'2  +  R"OH}}
:{{chem2|RCOCl + 2R'2NH → RC(O)NR'2  +  R'2NH2+Cl-}}
:{{chem2|(RCO)2O + R'2NH → RC(O)NR'2  +  RCO2H}}

[[Peptide synthesis]] use coupling agents such as [[HATU]], [[Hydroxybenzotriazole|HOBt]], or [[PyBOP]].<ref>{{cite journal|title=Amide bond formation: beyond the myth of coupling reagents |first1=Eric |last1=Valeur |first2=Mark |last2=Bradley |s2cid=14950926 |journal=Chem. Soc. Rev. |date=2009|volume=38 |issue=2 |pages=606–631 |doi=10.1039/B701677H|pmid=19169468 }}</ref>

===From nitriles===
The [[Nitrile#Hydrolysis|hydrolysis of nitriles]] is conducted on an industrial scale to produce fatty amides.<ref name=Ullmann>{{Ullmann|doi = 10.1002/14356007.a02_001.pub2|title =Amines, Aliphatic|year =2000|last1 =Eller|first1 =Karsten|last2 =Henkes|first2 =Erhard|last3 =Rossbacher|first3 =Roland|last4 =Höke|first4 =Hartmut}}</ref>  Laboratory procedures are also available.<ref>{{cite journal|last1=Wenner|first1=Wilhelm|title=Phenylacetamide|journal=Organic Syntheses|date=1952|volume=32|page=92|doi=10.15227/orgsyn.032.0092}}</ref>

===Specialty routes===
Many specialized methods also yield amides.<ref>{{cite journal|doi=10.1021/acs.chemrev.6b00237 |title=Nonclassical Routes for Amide Bond Formation |date=2016 |last1=De Figueiredo |first1=Renata Marcia |last2=Suppo |first2=Jean-Simon |last3=Campagne |first3=Jean-Marc |journal=Chemical Reviews |volume=116 |issue=19 |pages=12029–12122 |pmid=27673596 }}</ref> A variety of reagents, e.g. [[tris(2,2,2-trifluoroethyl) borate]] have been developed for specialized applications.<ref>{{Cite web|url=http://www.sigmaaldrich.com/catalog/product/aldrich/790877?lang=en&region=GB|title=Tris(2,2,2-trifluoroethyl) borate 97% {{!}} Sigma-Aldrich|website=www.sigmaaldrich.com|access-date=2016-09-22}}</ref><ref>{{Cite journal|last1=Sabatini|first1=Marco T.|last2=Boulton|first2=Lee T.|last3=Sheppard|first3=Tom D.|date=2017-09-01|title=Borate esters: Simple catalysts for the sustainable synthesis of complex amides|journal=Science Advances|volume=3|issue=9|pages=e1701028|doi=10.1126/sciadv.1701028|pmc=5609808|bibcode=2017SciA....3E1028S|pmid=28948222}}</ref>

{| class="wikitable sortable"
|+ Specialty Routes to Amides
|-
!Reaction name !! Substrate !! class="unsortable" | Details
|-
| [[Beckmann rearrangement]]
|Cyclic ketone
| Reagent: [[hydroxylamine]] and acid
|-
| [[Schmidt reaction]]
|Ketones
| Reagent: hydrazoic acid
|-
| [[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<ref>{{Cite journal|title=none|author =Bodroux F.|journal=Bull. Soc. Chim. France|year= 1905|volume= 33|pages= 831}}</ref><ref>{{cite web |title=Bodroux reaction |publisher=Institute of Chemistry, Skopje, Macedonia |url=http://www.pmf.ukim.edu.mk/PMF/Chemistry/reactions/bodroux1.htm |access-date=23 May 2007 |archive-date=24 September 2015 |archive-url=https://web.archive.org/web/20150924074536/http://www.pmf.ukim.edu.mk/PMF/Chemistry/reactions/bodroux1.htm |url-status=dead }}</ref>
| [[Carboxylic acid]], [[Grignard reagent]] with an [[aniline]] derivative ArNHR'
|style=background:white| [[File:Bodroux reaction.svg|400px]]
|-
|[[Chapman rearrangement]]<ref>{{Cite journal|last1=Schulenberg|first1=J. W.|last2=Archer|first2=S.|title=The Chapman Rearrangement|journal=[[Organic Reactions|Org. React.]]|year=1965|volume=14|pages=1–51 |doi=10.1002/0471264180.or014.01|isbn=978-0471264187 }}</ref><ref>{{Cite journal|doi=10.1039/CT9252701992|title=CCLXIX.—Imino-aryl ethers. Part III. The molecular rearrangement of ''N''-phenylbenziminophenyl ether |year=1925|last1=Chapman|first1=Arthur William|journal=Journal of the Chemical Society, Transactions|volume=127|pages=1992–1998}}</ref>
|Aryl [[imidate|imino ether]]
|For ''N'',''N''-diaryl amides. The [[reaction mechanism]] is based on a [[nucleophilic aromatic substitution]].<ref>{{Cite book|title=Advanced organic Chemistry, Reactions, mechanisms and structure|edition= 3rd |author =March, Jerry |isbn= 978-0-471-85472-2|year= 1966 |publisher= Wiley }}</ref>
|-
| [[Leuckart amide synthesis]]<ref>{{Cite journal|author = Leuckart, R. |journal=[[Berichte der deutschen chemischen Gesellschaft]]|doi=10.1002/cber.188501801182|title= Ueber einige Reaktionen der aromatischen Cyanate|year= 1885|volume= 18|pages= 873–877|author-link=Rudolf Leuckart (chemist)|url=https://zenodo.org/record/1425383}}</ref>
| [[Isocyanate]]
| Reaction of arene with isocyanate catalysed by [[aluminium trichloride]], formation of aromatic amide.
|-
| [[Ritter reaction]]<ref>{{cite book|last1=Adams|first1=Rodger|last2=Krimen|first2=L.I.|last3=Cota|first3=Donald J.|title=Organic Reaction Volume 17|date=1969|publisher=John Wiley & Sons, Inc|location=London|isbn=9780471196150|pages=213–326|doi=10.1002/0471264180}}</ref>
| [[Alkene]]s, [[Alcohol (chemistry)|alcohol]]s, or other [[carbonium ion]] sources
| [[Secondary (chemistry)|Secondary]] amides via an [[addition reaction]] between a [[nitrile]] and a carbonium ion in the presence of concentrated acids.
|-
| [[Photochemistry|Photolytic]] addition of [[formamide]] to [[olefins]]<ref>{{cite book|last=Monson|first=Richard|title=Advanced Organic Synthesis: Methods and Techniques|date=1971|publisher=Academic Press|location=New York|isbn=978-0124336803|page=141|url=https://nootropicsfrontline.com/wp-content/uploads/2021/07/wiki_Monson-R.S.-Advanced-organic-synthesis.-Methods-and-techniques-ГХИ-1971.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://nootropicsfrontline.com/wp-content/uploads/2021/07/wiki_Monson-R.S.-Advanced-organic-synthesis.-Methods-and-techniques-ГХИ-1971.pdf |archive-date=2022-10-09 |url-status=live}}</ref>
| [[Terminal alkene]]s
| A [[free radical]] [[homologation reaction]] between a terminal [[alkene]] and formamide.
|-
|Dehydrogenative coupling<ref>{{Cite journal|doi=10.1126/science.1145295|title=Direct Synthesis of Amides from Alcohols and Amines with Liberation of H<sub>2</sub>|year=2007|last1=Gunanathan|first1=C.|last2=Ben-David|first2=Y.|last3=Milstein|first3=D.|journal=Science|volume=317|issue=5839|pages=790–2|pmid=17690291|bibcode=2007Sci...317..790G|s2cid=43671648}}</ref>
|alcohol, amine
| requires [[organoruthenium compound|ruthenium dehydrogenation catalyst]]
|-
|[[Transamidation]]<ref>{{cite journal|author1=T. A. Dineen |author2=M. A. Zajac |author3=A. G. Myers|title=Efficient Transamidation of Primary Carboxamides by ''in situ'' Activation with N,N-Dialkylformamide Dimethyl Acetals|journal= J. Am. Chem. Soc.|volume=128|issue=50|pages=16406–16409|year=2006|doi=10.1021/ja066728i|pmid=17165798}}</ref><ref>{{cite journal|title=A two-step approach to achieve secondary amide transamidation enabled by nickel catalysis|author1=Emma L. Baker |author2=Michael M. Yamano |author3=Yujing Zhou |author4=Sarah M. Anthony |author5=Neil K. Garg|journal=Nature Communications|volume=7|pages=11554|year=2016|doi=10.1038/ncomms11554|pmid=27199089|pmc=4876455|bibcode=2016NatCo...711554B}}</ref>
|amide
|typically slow
|}

==See also==
* [[Amidogen]]
* [[Amino radical]]
* [[Amidicity]]
* [[Imidic acid]]
* [[Metal amides]]

==References==
{{reflist}}

==External links==
{{wikiquote}}
* [http://www.rsc.org/Chemsoc/Chembytes/IUPACGoldbook.asp IUPAC Compendium of Chemical Terminology]

{{nitrogen compounds}}
{{Functional groups}}
{{Organic reactions}}
{{Authority control}}

[[Category:Carboxamides| ]]
[[Category:Functional groups]]