Amide
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2008-06-25T16:11:45Z
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/* Naming conventions */
[[Image:Amide-general.png|right|thumb|right|200px|Amide functional group]]
[[Image:Formamide-MO-3D-balls.png|thumb|right|200px|Amides possess a [[conjugated system]] spread over the O, C and N atoms, consisting of [[molecular orbital]]s occupied by [[delocalized electron]]s. One of the [[pi bond|''π'' molecular orbitals]] in [[formamide]] is shown above.]]
In [[chemistry]], an '''amide''' is one of three kinds of [[compound]]s:
*(sometimes called acid amide) the [[organic chemistry|organic]] [[functional group]] characterized by a [[carbonyl]] group (C=O) linked to a [[nitrogen]] atom ([[N]]), or a compound that contains this functional group (pictured to the right); or
* a particular kind of nitrogen [[anion]].
* any organic compound derived by the replacement of a hydroxyl group by an amino group.
Amides are the most stable of all the carbonyl functional groups.
Many chemists make a pronunciation distinction between the two, saying ({{IPAEng|əˈmiːd}} for the [[carbonyl]]-[[nitrogen]] compound and {{IPA|/ˈæmɑɪd/}} for the [[anion]]. Others substitute one of these pronunciations with {{IPA|/ˈæmɨd/}}, while still others pronounce both {{IPA|/ˈæmɨd/}}, making them [[homonym]]s.
In the first sense referred to above, an amide is an [[amine]] where one of the [[nitrogen]] [[substituent]]s is an [[acyl]] group; it is generally represented by the formula: R<sub>1</sub>([[carbon|C]][[oxygen|O]])[[nitrogen|N]]R<sub>2</sub>R<sub>3</sub> , where either or both R<sub>2</sub> and R<sub>3</sub> may be [[hydrogen]]. Specifically, an amide can also be regarded as a derivative of a [[carboxylic acid]] in which the [[hydroxyl]] group has been replaced by an [[amine]] or [[ammonia]].<br />
Compounds in which a [[hydrogen]] [[atom]] on [[nitrogen]] from [[ammonia]] or an [[amine]] is replaced by a [[metal]] [[cation]] are also known as amides or '''azanides'''.
The second sense of the word ''amide'' is the amide [[anion]], which is a deprotonated form of [[ammonia]] (NH<sub>3</sub>) or an [[amine]]. It is generally represented by the formula: [R<sub>1</sub>NR<sub>2</sub>]<sup>-</sup>, and is an extremely strong [[Base (chemistry)|base]], due to the extreme weakness of [[ammonia]] and its [[Analog (chemistry)|analogue]]s as [[Brønsted acid]]s.
The remainder of this article is about the [[carbonyl]]-[[nitrogen]] sense of ''amide''. For examples of the [[anionic]] amide, see the articles [[Sodium amide]] and [[Lithium diisopropylamide]].
==Amide synthesis==<!-- This section is linked from [[Organic reaction]] -->
*Amides are commonly formed from the reaction of a [[carboxylic acid]] with an [[amine]]. This is the [[Chemical reaction|reaction]] that forms [[peptide bond]]s between [[amino acid]]s. These amides can participate in [[hydrogen bond]]ing as [[hydrogen bond]] [[acceptor]]s and [[donor]]s, but do not [[ion]]ize in [[aqueous solution]], whereas their parent [[acid]]s and amines are almost completely [[ion]]ized in [[solution]] at neutral [[pH]]. Amide formation plays a role in the [[Chemical synthesis|synthesis]] of some [[condensation polymer]]s, such as [[nylon]] and [[Aramid]] ([[Twaron]] / [[Kevlar]]). In biochemistry peptides are synthesized in [[solid phase peptide synthesis]]. The [[Schotten-Baumann reaction]] describes the formation of amides from amines and [[acid chloride]]s.
:[[Image:SimpleAmideFormationByCondensation.png|600px|Amide bond formation]]
* Cyclic amides are synthesized in the [[Beckmann rearrangement]] from oximes.
* Amides also form from ketones and hydrazoic acid in the [[Schmidt reaction]]
* Amides can be prepared from aryl alkyl ketones, sulfur and morpholine in the [[Willgerodt-Kindler reaction]]
* Other amide-forming multicomponent [[Chemical reaction|reaction]]s are the [[Passerini reaction]] and the [[Ugi reaction]]
* In the '''Bodroux reaction''' an amide RNHCOR' is synthesized from a [[carboxylic acid]] R-COOH and the adduct of a [[Grignard reagent]] with an [[aniline]] derivative ArNHR' <ref>Bodroux F., Bull. Soc. Chim. France, 1905, 33, 831;</ref> <ref> Bodroux reaction at the Institute of Chemistry, Skopje, Macedonia [http://www.pmf.ukim.edu.mk/PMF/Chemistry/reactions/bodroux1.htm Link]</ref>
* In the '''Chapman rearrangement''' (first reported in 1925) an aryl [[imidate|imino ether]] is converted to a N,N-diaryl amide:
:[[Image:ChapmanRearrangementE.svg|Chapman rearrangement]]
:The [[reaction mechanism]] is based on a [[nucleophilic aromatic substitution]]. <ref>''Advanced organic Chemistry, Reactions, mechanisms and structure'' 3ed. Jerry March ISBN 0-471-85472-7 </ref>
* The seemingly simple direct reaction between an [[alcohol]] and an [[amine]] to an amide was not tried until 2007 when a special [[ruthenium]]-based [[catalyst]] was reported be effective in a so-called '''dehydrogenative acylation''' <ref>''Direct Synthesis of Amides from Alcohols and Amines with Liberation of H2'' Chidambaram Gunanathan, Yehoshoa Ben-David, David Milstein Science 10 August 2007: Vol. 317. no. 5839, pp. 790 - 792 {{DOI|10.1126/science.1145295}}</ref>:
:[[Image:DehydrogenativeAmidation.svg|Synthesis of Amides from Alcohols and Amines with Liberation of H2]]
:The generation of hydrogen gas compensates for unfavorable the thermodynamics. The reaction is believed to proceed by one dehydrogenation of the alcohol to the [[aldehyde]] followed by formation of a [[hemiaminal]] and the after a second dehydrogenation to the amide. Elimination of water in the hemiaminal to the imine is not observed.
== Amide reactions ==<!-- This section is linked from [[Organic reaction]] -->
* Amide breakdown is possible via [[amide hydrolysis]]. Such hydrolysis can occur under basic or acidic conditions. Acidic conditions yield the carboxylic acid and the ammonium ion while basic hydrolysis yield the carboxylate ion and ammonia.
* In the [[Vilsmeier-Haack reaction]] an amide is converted into an [[imine]].
* [[Hofmann rearrangement]] of primary amides to primary [[amine]]s.
Owing to their resonance stabilization, amides are relatively unreactive under physiological conditions, even less than similar compounds such as [[ester]]s. Nevertheless, amides can undergo chemical reactions, usually through an attack of an [[electronegativity|electronegative]] atom on the [[carbonyl]] [[carbon]], breaking the carbonyl double bond and forming a tetrahedral intermediate. When the functional group attacking the amide is a [[thiol]], [[hydroxyl]] or [[amine]], the resulting molecule may be called a [[cyclol]] or, more specifically, a thiacyclol, an oxacyclol or an azacyclol, respectively.
The proton of an amide does not dissociate readily under normal conditions; its p''K<sub>a</sub>'' is usually well above 15. However, under extremely acidic conditions, the carbonyl [[oxygen]] can become protonated with a p''K<sub>a</sub>'' of roughly -1.
Amides will react with [[nitrous acid]] (HONO) forming the carboxylic acid and yielding nitrogen. Nitrous acid is formed by addition of a strong acid to a nitrate (III) salt in solution at temperatures of between 0 and 10 degrees.
Amides undergo the [[Hofmann rearrangement]] in which an amine with one less carbon atom is produced upon reaction with bromine and sodium hydroxide. On the other hand, reacting the amide with the strong reducing agent [[lithium aluminium hydride]] yields an amine with the same number of carbon atoms.
Amides are dehydrated with phosphorus (V) oxide forming the nitrile. Care should be taken when performing such a reaction since phosphorus (V) oxide smoulders when in contact with organic matter.
== Amide linkage (peptide bond) ==
An amide linkage is kinetically stable to [[hydrolysis]]. However, it can be hydrolysed in boiling [[alkali]], as well as in strong [[acid]]ic conditions. Amide linkages in a [[biochemistry|biochemical]] context are called [[peptide link]]ages. Amide linkages constitute a defining molecular feature of [[protein]]s, the [[secondary structure]] of which is due in part to the [[hydrogen bonding]] abilities of amides.
== Amide properties ==
[[Image:AmideResonance.png|right|400px|Amide resonance:]]Compared to [[amine]]s, amides are very weak [[Base (chemistry)|base]]s. 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 amides don't have as clearly noticeable [[acid-base]] properties in [[water]]. This lack of basicity is explained by the [[electron]]-withdrawing nature of the [[carbonyl group]] where the lone pair of [[electron]]s on the [[nitrogen]] is delocalized by [[resonance (chemistry)|resonance]], thus forming a partial [[double bond]] with the [[carbonyl]] [[carbon]] and putting a negative charge on the [[oxygen]]. On the other hand, amides are much stronger [[Base (chemistry)|base]]s than [[carboxylic acid]]s, [[ester]]s, [[aldehyde]]s, and [[ketone]]s (conjugated acid pKa between -6 and -10). It is estimated [[in silico]] that [[acetamide]] is represented by [[resonance structure]] A for 62% and by B for 28% <ref>''"Amide Resonance" Correlates with a Breadth of C-N Rotation Barriers'' Carl R. Kemnitz and Mark J. Loewen [[J. Am. Chem. Soc.]]; '''2007'''; 129(9) pp 2521 - 2528; (Article) {{DOI|10.1021/ja0663024}}</ref>. Resonance is largely prevented in the very strained [[quinuclidone]].
== Solubility ==
Amides contain carbonyl (C=O) and ether (N-C) dipoles arising from covalent bonding between electronegative oxygen and nitrogen atoms and electro-neutral carbon atoms. Primary and secondary amides also contain two- and one N-H dipoles, respectively. Because of the pi-bonding arrangement of the carbonyl and the greater electronegativity of oxygen, 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 and nitrogen atoms 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
While hydrogen bonding may enhance the water solubility of amides relative to hydrocarbons (alkanes, alkenes, alkynes and aromatic compounds), amides typically are regarded as compounds with low water solubility. They are significantly less water soluble than comparable acids or alcohols due to:
1). their non-ionic character
2). the presence of nonpolar hydrocarbon functionality, and
3). the inability of tertiary amides to donate hydrogen bonds to water (they can only be H-bond acceptors).
Thus amides have water solubilities roughly comparable to esters. Typically amides are less soluble than comparable amines and carboxylic acids since these compounds can both donate and accept hydrogen bonds, and can ionize at appropriate pHs to further enhance solubility
==Derivatives==
[[Sulfonamide (chemistry)|Sulfonamide]]s are [[Analog (chemistry)|analogue]]s of amides in which the atom double-bonded to [[oxygen]] is [[sulfur]] rather than [[carbon]].
Cyclic amides are called [[lactam]]s.
==Naming conventions ==
*Example: CH<sub>3</sub>CONH<sub>2</sub> is named [[acetamide]] or [[ethanamide]]
*Other examples: propan-1-amide, N,N-dimethylpropanamide, [[acrylamide]]
*For more detail see [[IUPAC nomenclature of organic chemistry#Amines and Amides|IUPAC nomenclature of organic chemistry - Amines and Amides]]
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==References==
{{reflist}}
==External links ==
*[http://www.chemsoc.org/chembytes/goldbook/ IUPAC Compendium of Chemical Terminology]
{{Functional Groups}}
[[Category:Amides| ]]
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