Editing Amide (section)

==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
|}