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{{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|FormamideFormamideFile:Asparagine w functional group highlighted.png|thumb|right|Asparagine (zwitterionic form), an amino acidamino acidIn organic chemistry, an amide,WEB,weblink Amide definition and meaning - Collins English Dictionary, www.collinsdictionary.com, 15 April 2018, {{AHDict|amide}}WEB,weblinkweblink" title="web.archive.org/web/20150402184403weblink">weblink dead, 2 April 2015, amide - Definition of amide in English by Oxford Dictionaries, Oxford Dictionaries – English, 15 April 2018, also known as an organic amide or a carboxamide, is a compound with the general formula {{chem2|RsC(dO)sNR′R″}}, where R, R', and R″ represent any group, typically organyl groups or hydrogen atoms.{{goldbookref|file=A00266|title=amides}}BOOK, John H., Fletcher, Chapter 21: Amides and Imides, Nomenclature of Organic Compounds: Principles and Practice, 166–173, 10.1021/ba-1974-0126.ch021, 126, 9780841201910,weblink Washington, DC, American Chemical Society, 1974, The amide group is called a peptide bond when it is part of the 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 of a carboxylic acid ({{chem2|RsC(dO)sOH}}) with the hydroxyl group ({{chem2|sOH}}) replaced by an amine group ({{chem2|sNR′R″}}); or, equivalently, an acyl (alkanoyl) group ({{chem2|RsC(dO)s}}) joined to an amine group.Common of amides are formamide ({{chem2|HsC(dO)sNH2}}), acetamide ({{chem2|H3CsC(dO)sNH2}}), benzamide ({{chem2|C6H5sC(dO)sNH2}}), and dimethylformamide ({{chem2|HsC(dO)sN(sCH3)2}}). Some uncommon examples of amides are N-chloroacetamide ({{chem2|H3CsC(dO)sNHsCl}}) and chloroformamide ({{chem2|ClsC(dO)sNH2}}).Amides are qualified as primary, secondary, and tertiary according to whether the amine subgroup has the form {{chem2|sNH2}}, {{chem2|sNHR}}, or {{chem2|sNRR'}}, where R and R' are groups other than hydrogen.

Nomenclature

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 (CH3CONH2). 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 (CH3CONMe2, where Me = CH3). Usually even this name is simplified to dimethylacetamide. Cyclic amides are called lactams; they are necessarily secondary or tertiary amides.{{BlueBook2004|rec=66.1}} Full text (PDF) of Draft Rule P-66: Amides, Imides, Hydrazides, Nitriles, Aldehydes, Their Chalcogen Analogues, and Derivatives

Applications

{{See also|polyamide|peptide bond}}Amides are pervasive in nature and technology. Proteins and important plastics like Nylons, Aramid, Twaron, and Kevlar are polymers whose units are connected by amide groups (polyamides); these linkages are easily formed, confer structural rigidity, and resist hydrolysis. Amides include many other important biological compounds, as well as many drugs like paracetamol, penicillin and LSD.JOURNAL, 10.1016/j.jep.2012.05.038, Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides, 2012, Boonen, Jente, Bronselaer, Antoon, Nielandt, Joachim, Veryser, Lieselotte, De Tré, Guy, De Spiegeleer, Bart, Journal of Ethnopharmacology, 142, 3, 563–590, 22659196, 1854/LU-2133714,weblinkweblink 2022-10-09, live, free, 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-bonded dimer from (X-ray crystallography]]. Selected distances: C-O: 1.243, C-N, 1.325, N---O, 2.925 Ã…. Color code: red = O, blue = N, gray = C, white = H.JOURNAL, 10.1107/S1600536803019494, A new refinement of the orthorhombic polymorph of acetamide, 2003, Bats, Jan W., Haberecht, Monika C., Wagner, Matthias, Acta Crystallographica Section E, 59, 10, o1483–o1485, )The lone pair of electrons 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 orbitals occupied by delocalized electrons, forming a conjugated system. Consequently, the three bonds of the nitrogen in amides is not pyramidal (as in the amines) 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)NR2 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 between two alternative structures: neutral (A) and zwitterionic (B). 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.JOURNAL, 10.1021/ja0663024, "Amide Resonance" Correlates with a Breadth of C−N Rotation Barriers, 2007, Kemnitz, Carl R., Loewen, Mark J., Journal of the American Chemical Society, 129, 9, 2521–8, 17295481, Resonance is largely prevented in the very strained quinuclidone.In their IR spectra, amides exhibit a moderately intense νCO band near 1650 cm−1. The energy of this band is about 60 cm-1 lower than for the νCO of esters and ketones. This difference reflects the contribution of the zwitterionic resonance structure.

Basicity

Compared to amines, amides are very weak bases. While the conjugate acid of an amine has a pKa of about 9.5, the conjugate acid of an amide has a pKa 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 bases than carboxylic acids, esters, aldehydes, and ketones (their conjugate acids' pKas are between −6 and −10).The proton of a primary or secondary amide does not dissociate readily; its pKa is usually well above 15. Conversely, under extremely acidic conditions, the carbonyl oxygen can become protonated with a pKa 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 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 N,N-dimethylformamide, exhibit low solubility in water.

Reactions

Amides undergo many chemical reactions, although they are less reactive than esters. Amides hydrolyse in hot alkali as well as in strong acidic 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. Amides are also versatile precursors to many other functional groups. Electrophiles react with the carbonyl oxygen. This step often precedes hydrolysis, which is catalyzed by both Brønsted acids and Lewis acids. Enzymes, e.g. peptidases and artificial catalysts, are known to accelerate the hydrolysis reactions.{| class="wikitable sortable" style="background-color:white;float: center; border-collapse: collapse; margin: 0em 1em;" border="1" cellpadding="2" cellspacing="0"! width=200px|Reaction name !! Product !! class="unsortable" | Comment

Dehydration	Nitrile	phosphorus pentoxide; benzenesulfonyl chloride; TFAA/pyridine>py{{US patent|5935953}}

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)

POCl3}}, aromatic substrate, formamide

|Bischler–Napieralski reaction|Cyclic aryl imine

Phosphoryl chloride>{{chem2	, SOCl2}}, etc.

Darzens reaction>Tautomeric chlorination	Imidoyl chloride	Oxophilic halogenating agents, e.g. Phosgene	or Thionyl chloride>SOCl2

Synthesis

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: Esters are far superior substrates relative to carboxylic acids.JOURNAL, Corson, B. B., Scott, R. W., Vose, C. E., Cyanoacetamide, Organic Syntheses, 1941, 1, 179, 10.15227/orgsyn.009.0036, JOURNAL, Jacobs, W. A., Chloroacetamide, Organic Syntheses, 1941, 1, 153, 10.15227/orgsyn.007.0016, JOURNAL, Kleinberg, J., Audrieth, L. F., Lactamide, Organic Syntheses, 1955, 3, 516, 10.15227/orgsyn.021.0071, Further "activating" both acid chlorides (Schotten-Baumann reaction) and anhydrides (Lumière–Barbier method) react with amines to give amides: Peptide synthesis use coupling agents such as HATU, HOBt, or PyBOP.JOURNAL, Amide bond formation: beyond the myth of coupling reagents, Eric, Valeur, Mark, Bradley, 14950926, Chem. Soc. Rev., 2009, 38, 2, 606–631, 10.1039/B701677H, 19169468,

From nitriles

The hydrolysis of nitriles is conducted on an industrial scale to produce fatty amides.{{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}} Laboratory procedures are also available.JOURNAL, Wenner, Wilhelm, Phenylacetamide, Organic Syntheses, 1952, 32, 92, 10.15227/orgsyn.032.0092,

Specialty routes

Many specialized methods also yield amides.JOURNAL, 10.1021/acs.chemrev.6b00237, Nonclassical Routes for Amide Bond Formation, 2016, De Figueiredo, Renata Marcia, Suppo, Jean-Simon, Campagne, Jean-Marc, Chemical Reviews, 116, 19, 12029–12122, 27673596, A variety of reagents, e.g. tris(2,2,2-trifluoroethyl) borate have been developed for specialized applications.WEB,weblink Tris(2,2,2-trifluoroethyl) borate 97% {{!, Sigma-Aldrich|website=www.sigmaaldrich.com|access-date=2016-09-22}}JOURNAL, Sabatini, Marco T., Boulton, Lee T., Sheppard, Tom D., 2017-09-01, Borate esters: Simple catalysts for the sustainable synthesis of complex amides, Science Advances, 3, 9, e1701028, 10.1126/sciadv.1701028, 5609808, 2017SciA....3E1028S, 28948222, {| class="wikitable sortable" style="background-color:white;float: center; border-collapse: collapse; margin: 0em 1em;" border="1" cellpadding="2" cellspacing="0"|+ Specialty Routes to Amides! width=200px|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|

	JOURNAL=BULL. SOC. CHIM. FRANCE	VOLUME= 33		URL=HTTP://WWW.PMF.UKIM.EDU.MK/PMF/CHEMISTRY/REACTIONS/BODROUX1.HTM	ARCHIVE-DATE=24 SEPTEMBER 2015	URL-STATUS=DEAD, | Carboxylic acid, Grignard reagent with an aniline derivative ArNHR'	400px)

Chapman rearrangementSCHULENBERG

LAST2=ARCHER

TITLE=THE CHAPMAN REARRANGEMENT

ORGANIC REACTIONS>ORG. REACT.

VOLUME=14

DOI=10.1002/0471264180.OR014.01

N-PHENYLBENZIMINOPHENYL ETHER >YEAR=1925

FIRST1=ARTHUR WILLIAM

VOLUME=127, 1992–1998,

imidate>imino ether

N,N-diaryl amides. The reaction mechanism is based on a nucleophilic aromatic substitution.ADVANCED ORGANIC CHEMISTRY, REACTIONS, MECHANISMS AND STRUCTURE

AUTHOR =MARCH, JERRY

YEAR= 1966, Wiley,

Leuckart amide synthesisLEUCKART, R.	BERICHTE DER DEUTSCHEN CHEMISCHEN GESELLSCHAFT>DOI=10.1002/CBER.188501801182	YEAR= 1885	PAGES= 873–877	URL=HTTPS://ZENODO.ORG/RECORD/1425383, | Isocyanate| Reaction of arene with isocyanate catalysed by aluminium trichloride, formation of aromatic amide.

Ritter reactionADAMS	LAST2=KRIMEN	LAST3=COTA	TITLE=ORGANIC REACTION VOLUME 17	PUBLISHER=JOHN WILEY & SONS, INC	ISBN=9780471196150	DOI=10.1002/0471264180,	Alkenes, Alcohol (chemistry)>alcohols, 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 olefinsMONSON>FIRST=RICHARD	DATE=1971	LOCATION=NEW YORK	PAGE=141	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	URL-STATUS=LIVE, | Terminal alkenes| A free radical homologation reaction between a terminal alkene and formamide.

	YEAR=2007	FIRST1=C.	FIRST2=Y.	FIRST3=D.	VOLUME=317	PAGES=790–2	BIBCODE=2007SCI...317..790G, 43671648, |alcohol, amine	organoruthenium compound>ruthenium dehydrogenation catalyst

TransamidationT. A. DINEEN	AUTHOR3=A. G. MYERS	IN SITU ACTIVATION WITH N,N-DIALKYLFORMAMIDE DIMETHYL ACETALS>JOURNAL= J. AM. CHEM. SOC.	ISSUE=50	YEAR=2006	PMID=17165798, A TWO-STEP APPROACH TO ACHIEVE SECONDARY AMIDE TRANSAMIDATION ENABLED BY NICKEL CATALYSIS>AUTHOR1=EMMA L. BAKER	AUTHOR3=YUJING ZHOU	AUTHOR5=NEIL K. GARG	VOLUME=7	YEAR=2016	PMID=27199089	BIBCODE=2016NATCO...711554B, |amide|typically slow

	AUTHOR3=J. S. MANZANO	AUTHOR5=A. D. SADOW	TITLE=SURFACE LIGANDS ENHANCE THE CATALYTIC ACTIVITY OF SUPPORTED AU NANOPARTICLES FOR THE AEROBIC α-OXIDATION OF AMINES TO AMIDES	VOLUME=12	PAGES=1922–1933	DOI=10.1039/D1CY02121D	DOI-ACCESS=FREE, |alkyl amine| requires gold catalysts

See also

• Amidogen
• Amino radical
• Amidicity
• Imidic acid
• Metal amides

References

{{reflist}}

External links

• IUPAC Compendium of Chemical Terminology

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