Editing Acyl group

{{Short description|1=Chemical group (R–C=O)}}
[[File:Acyl group V.0.svg|thumb|400px|A general acyl group (<span style="color:blue;">'''blue'''</span>) in a [[ketone]] (top left), as an acylium [[cation]] (top centre), as an acyl [[Radical (chemistry)|radical]] (top right), an [[aldehyde]] (bottom left), [[ester]] (bottom centre) or [[amide]] (bottom right). ({{chem2|R^{1}, R^{2} and R^{3}|}} stands for [[organyl]] substituent or [[hydrogen]] in the case of {{chem2|R^{1}|}})]]

In [[chemistry]], an '''acyl group''' is a [[moiety (chemistry)|moiety]] derived by the removal of one or more [[hydroxyl]] groups from an [[oxoacid]],<ref name="gold book">{{GoldBookRef|file=A00123|title=Acyl groups|accessdate=January 18, 2014}}</ref> including [[inorganic acid]]s. It contains a double-bonded [[oxygen]] [[atom]] and an [[organyl group]] ({{chem2|R\sC\dO}}) or [[hydrogen]] in the case of [[formyl group]] ({{chem2|H\sC\dO}}). In [[organic chemistry]], the acyl group ([[IUPAC]] name '''alkanoyl''' if the organyl group is [[alkyl]]) is usually derived from a [[carboxylic acid]], in which case it has the formula {{chem2|R\sC(\dO)\s}}, where R represents an [[organyl]] group or [[hydrogen]]. Although the term is almost always applied to organic compounds, acyl groups can in principle be derived from other types of acids such as [[sulfonic acid]]s and [[phosphonic acid]]s. In the most common arrangement, acyl groups are attached to a larger molecular fragment, in which case the carbon and oxygen atoms are linked by a [[double bond]].

==Reactivity trends==
There are five main types of acyl derivatives. [[Acid halide]]s are the most reactive towards nucleophiles, followed by [[anhydride]]s, [[ester]]s, and [[amide]]s. [[Carboxylate]] ions are essentially unreactive towards nucleophilic substitution, since they possess no leaving group. The reactivity of these five classes of compounds covers a broad range; the relative reaction rates of acid chlorides and amides differ by a factor of 10<sup>13</sup>.<ref name=carey>{{cite book|last=Carey|first=Francis A.|title=Organic Chemistry|year=2006|publisher=McGraw-Hill|location=New York|isbn=0072828374|pages=[https://archive.org/details/organicchemistry6th00care/page/866 866–868]|edition=6th|url=https://archive.org/details/organicchemistry6th00care/page/866}}</ref>

:[[File:Reactivity of Carboxylic Acid Derivatives Towards Nucleophiles.png|Acid chlorides are most reactive towards nucleophiles, followed by anhydrides, esters, amides, and carboxylate anions.|590px]]

A major factor in determining the reactivity of acyl derivatives is leaving group ability, which is related to acidity. Weak bases are better leaving groups than strong bases; a species with a strong [[conjugate acid]] (e.g. [[hydrochloric acid]]) will be a better leaving group than a species with a weak conjugate acid (e.g. [[acetic acid]]). Thus, [[chloride]] ion is a better leaving group than [[acetate ion]]. The reactivity of acyl compounds towards nucleophiles decreases as the basicity of the leaving group increases, as the table shows.<ref name=wade3>Wade 2010, pp. 998–999.</ref>

{| class="wikitable"
|-
! Compound Name
! Structure
! Leaving Group
! width="120" | p''K<sub>a</sub>'' of Conjugate Acid
|-
| [[Acetyl chloride]]
| [[File:Acetyl-chloride_skeletal.svg|center|60px]]
| [[File:Chloride.png|center|34px]]
| −7
|-
| [[Acetic anhydride]]
| [[File:Acetic anhydride2DACS.svg|center|96px]]
| [[File:Acetate anion.png|center|69px]]
| 4.76
|-
| [[Ethyl acetate]]
| [[File:Ethyl-acetate-2D-skeletal.svg|center|96px]]
| [[File:Ethoxide.png|center|69px]]
| 15.9
|-
| [[Acetamide]]
| [[File:Acetamide-2D-skeletal.png|center|77px]]
| [[File:Amide anion.png|center|48px]]
| 38
|-
| [[Acetate]] anion 
| [[File:Acetate anion.png|center|69px]]
| N/a
| N/a
|-
|}

[[File:Resonance Forms of an Amide.png|thumb|264px|The two major resonance forms of an amide.]] Another factor that plays a role in determining the reactivity of acyl compounds is [[resonance (chemistry)|resonance]]. Amides exhibit two main resonance forms. Both are major contributors to the overall structure, so much so that the amide bond between the carbonyl carbon and the amide nitrogen has significant [[double bond]] character. The [[activation energy|energy barrier]] for rotation about an amide bond is 75–85 kJ/mol (18–20 kcal/mol), much larger than values observed for normal single bonds. For example, the C–C bond in ethane has an energy barrier of only 12 kJ/mol (3 kcal/mol).<ref name=carey /> Once a nucleophile attacks and a tetrahedral intermediate is formed, the energetically favorable resonance effect is lost. This helps explain why amides are one of the least reactive acyl derivatives.<ref name=wade3 />

Esters exhibit less resonance stabilization than amides, so the formation of a tetrahedral intermediate and subsequent loss of resonance is not as energetically unfavorable. Anhydrides experience even weaker resonance stabilization, since the resonance is split between two carbonyl groups, and are more reactive than esters and amides. In acid halides, there is very little resonance, so the energetic penalty for forming a tetrahedral intermediate is small. This helps explain why acid halides are the most reactive acyl derivatives.<ref name=wade3 />

==Compounds==
Well-known acyl compounds are the [[acyl chloride]]s, such as [[acetyl chloride]] (CH<sub>3</sub>COCl) and [[benzoyl chloride]] (C<sub>6</sub>H<sub>5</sub>COCl). These compounds, which are treated as sources of acylium cations, are good [[reagent]]s for attaching acyl groups to various substrates. [[Amide]]s ('''RC(O)'''NR′<sub>2</sub>) and [[ester]]s ('''RC(O)'''OR′) are classes of acyl compounds, as are [[ketone]]s ('''RC(O)'''R′) and [[aldehyde]]s ('''RC(O)'''H), where R and R′ stand for [[organyl]] (or [[hydrogen]] in the case of [[formyl]]).

==Acylium cations, radicals, and anions==
[[File:Acylium.svg|thumb|150px|Resonance structures of acylium ion]]
Acylium ions are [[cation]]s of the formula {{chem2|RCO+}}.<ref>{{GoldBookRef|file=A00129|title=Acyl species|accessdate=January 18, 2014}}</ref> The carbon–oxygen [[bond length]] in these cations is near 1.1&nbsp;[[Ångström|Å]] (110-112 pm), which is shorter than the 112.8 pm of [[carbon monoxide]] and indicates [[triple bond|triple-bond]] character.<ref>{{cite journal |last1= Chevrier |first1= B. |last2= Carpentier |first2= J. M. Le |last3= Weiss |first3= R. |year= 1972 |title= Synthesis of two crystalline species of the Friedel–Crafts intermediate antimony pentachloride-''p''-toluoyl chloride. Crystal structures of the donor–acceptor complex and of the ionic salt |journal= J. Am. Chem. Soc. |volume= 94 |issue= 16 |pages= 5718–5723 |doi= 10.1021/ja00771a031}}</ref><ref>{{ cite journal | title = Structural effects of carbon monoxide coordination to carbon centers. π and σ bindings in aliphatic acyl versus aromatic aroylcations | first1 = Milya G. | last1 = Davlieva | first2 = Sergey V. | last2 = Lindeman | first3 = Ivan S. | last3 = Neretin | first4 = Jay K. | last4 = Kochi | journal = [[New Journal of Chemistry|New J. Chem.]] | year = 2004 | volume = 28 | pages = 1568–1574 | doi = 10.1039/B407654K }}</ref><ref>{{ cite journal | title = Silicon Tetrakis(trifluoromethanesulfonate): A Simple Neutral Silane Acting as a Soft and Hard Lewis Superacid | first1 = André | last1 = Hermannsdorfer | first2 = Matthias | last2 = Driess | journal = [[Angewandte Chemie International Edition|Angew. Chem. Int. Ed.]] | volume = 60 | issue = 24 | year = 2021 | pages = 13656–13660 | doi = 10.1002/anie.202103414 | pmid = 33826216 | pmc = 8252640 | doi-access = free }}</ref>

The carbon centres of acylium ions generally have a [[linear molecular geometry|linear geometry]] and sp [[orbital hybridisation|atomic hybridization]], and are best represented by a [[resonance (chemistry)|resonance structure]] bearing a formal positive charge on the oxygen (rather than carbon): {{chem2|[R\sC\tO+]}}. They are characteristic fragments observed in EI-[[mass spectra]] of [[ketone]]s.

Acylium ions are common reactive intermediates, for example in the [[Friedel–Crafts acylation]] and many other [[organic reaction]]s such as the [[Hayashi rearrangement]]. Salts containing acylium ions can be generated by removal of the halide from [[acyl halide]]s:

:{{chem2 | RC(O)Cl + SbCl5 -> [RCO]+[SbCl6]- }}

Acyl [[radical (chemistry)|radical]]s are readily generated from aldehydes by hydrogen-atom abstraction. However, they undergo rapid [[decarbonylation]] to afford the alkyl radical:<ref>{{Cite book|title=March's Advanced Organic Chemistry|last=Smith|first=Michael B.|publisher=Wiley|year=2013|isbn=978-0-470-46259-1|location=Hoboken, NJ|pages=857}}</ref>

:{{chem2 | RC(H)\dO -> RC^{•}\dO -> R^{•} + C\tO }}

Acyl [[anion]]s are almost always unstable—usually too unstable to be exploited synthetically. They readily react with the neutral aldehyde to form an [[acyloin]] dimer. Hence, synthetic chemists have developed various acyl anion [[synthon|synthetic equivalent]]s, such as [[dithiane]]s, as surrogates. However, as a partial exception, hindered dialkylformamides (e.g., diisopropylformamide, HCON''i''Pr<sub>2</sub>) can undergo deprotonation at low temperature (−78&nbsp;°C) with [[lithium diisopropylamide]] as the base to form a [[carbamoyl]] anion stable at these temperatures.<ref>{{Cite journal|last1=Fraser|first1=Robert R.|last2=Hubert|first2=Patrick R.|date=1974-01-01|title=Direct Formation of the Carbonyl Anion of Diisopropyl Formamide|journal=Canadian Journal of Chemistry|volume=52|issue=1|pages=185–187|doi=10.1139/v74-029|issn=0008-4042|doi-access=free}}</ref>

==In biochemistry==
In [[biochemistry]] there are many instances of acyl groups, in all major categories of biochemical molecules.

[[Acyl-CoA]]s are acyl derivatives formed via [[fatty acid]] metabolism. [[Acetyl-CoA]], the most common derivative, serves as an acyl donor in many biosynthetic transformations. Such acyl compounds are [[thioester]]s.

Names of acyl groups of [[amino acid]]s are formed by replacing the ''-ine'' suffix with ''-yl''. For example, the acyl group of [[glycine]] is [[glycyl]], and of [[lysine]] is [[lysyl]].

Names of acyl groups of [[ribonucleoside monophosphate]]s such as [[adenosine monophosphate|AMP]] (5′-adenylic acid), [[guanosine monophosphate|GMP]] (5′-guanylic acid), [[cytidine monophosphate|CMP]] (5′-cytidylic acid), and [[uridine monophosphate|UMP]] (5′-uridylic acid) are adenylyl, guanylyl, cytidylyl, and uridylyl respectively.

In [[phospholipid]]s, the acyl group of [[phosphatidic acid]] is called phosphatidyl-.

Finally, many [[saccharide]]s are acylated.

==In organometallic chemistry and catalysis==
{{main|Transition metal acyl complexes}}
Acyl [[ligand]]s are intermediates in many [[carbonylation]] reactions, which are important in some catalytic reactions. Metal acyls arise usually via insertion of [[carbon monoxide]] into metal–[[alkyl]] bonds. Metal acyls also arise from reactions involving acyl chlorides with low-valence metal complexes or by the reaction of organolithium compounds with metal carbonyls. Metal acyls are often described by two resonance structures, one of which emphasizes the [[Base (chemistry)|basicity]] of the oxygen center. ''O''-alkylation of metal acyls gives [[Fischer carbene]] complexes.<ref>{{cite book|last=Elschenbroich |first=C. |title=Organometallics |date=2006 |publisher=Wiley-VCH |location=Weinheim |isbn=3-527-29390-6}}</ref>

==Nomenclature==
The [[trivial name|common name]]s of acyl groups are derived typically by replacing the '''-ic acid''' suffix of the corresponding [[carboxylic acid]]'s common name with '''-yl''' (or '''-oyl'''), as shown in the table below.

In the [[IUPAC nomenclature of organic chemistry]], the [[systematic name]]s of acyl groups are derived exactly by replacing the '''-yl''' suffix of the corresponding [[hydrocarbyl]] group's systemic name (or the '''-oic acid''' suffix of the corresponding [[carboxylic acid]]'s systemic name) with '''-oyl''', as shown in the table below.

The acyls are between the hydrocarbyls and the carboxylic acids.

The [[hydrocarbyl]] group names that end in -yl are not acyl groups, but [[alkyl]] groups derived from [[alkane]]s ([[methyl group|methyl]], [[ethyl group|ethyl]], [[propyl group|propyl]], [[butyl group|butyl]]), alkenyl groups derived from [[alkene]]s ([[propenyl]], butenyl), or [[aryl]] groups ([[benzyl group|benzyl]]).

{| class="wikitable"
!colspan="2"|Corresponding [[hydrocarbyl]] group name<br>RC–
!colspan="2"|Acyl group name<br>RC(O)–
!colspan="2"|Corresponding [[carboxylic acid]] name<br>RC(O)O-H
|-
!common!!systematic!!common!!systematic!!common!!systematic
|-
|align="center"|[[methyl group|methyl]]||align="center"|methanyl||[[formyl|form'''yl''']]||methanoyl|methan'''oyl'''||[[formic acid|form'''ic''' acid]]||methan'''oic''' acid
|-
|align="center"|[[ethyl group|ethyl]]||align="center"|ethanyl||[[acetyl group|acet'''yl''']]||ethanoyl|ethan'''oyl'''||[[acetic acid|acet'''ic''' acid]]||ethan'''oic''' acid
|-
|align="center"|[[propyl group|propyl]]||align="center"|propanyl||propion'''yl'''||propanoyl|propan'''oyl'''||[[propionic acid|propion'''ic''' acid]]||propan'''oic''' acid
|-
|align="center"|[[butyl group|butyl]]||align="center"|butanyl||butyr'''yl'''||butanoyl|butan'''oyl'''||[[butyric acid|butyr'''ic''' acid]]||butan'''oic''' acid
|-
|colspan="2" align="center"|[[propenyl]]||acryl'''yl''' or [[acryloyl group|acryl'''oyl''']]|||propen'''oyl'''||[[acrylic acid|acryl'''ic''' acid]]||propen'''oic''' acid
|-
|align="center"|[[crotyl]]||align="center"|butenyl||[[crotonyl|croton'''yl''']]||buten'''oyl'''||[[crotonic acid|croton'''ic''' acid]]||[[butenoic acid|buten'''oic''' acid]]
|-
|colspan="2" align="center"|[[benzyl group|benzyl]]||colspan="2" align="center"|[[benzoyl group|benz'''oyl''']]||colspan="2" align="center"|[[benzoic acid|benz'''oic''' acid]]
|}

==Reaction mechanisms==
Acyl compounds react with nucleophiles via an addition mechanism: the nucleophile attacks the carbonyl carbon, forming a [[tetrahedral intermediate]]. This reaction can be accelerated by [[acid]]ic conditions, which make the carbonyl more [[electrophile|electrophilic]], or [[base (chemistry)|basic]] conditions, which provide a more [[anion]]ic and therefore more reactive nucleophile. The tetrahedral intermediate itself can be an alcohol or [[alkoxide]], depending on the [[pH]] of the reaction.

The tetrahedral intermediate of an [[acyl]] compound contains a [[substituent]] attached to the central carbon that can act as a [[leaving group]]. After the tetrahedral intermediate forms, it collapses, recreating the carbonyl C=O bond and ejecting the leaving group in an [[elimination reaction]]. As a result of this two-step addition/elimination process, the nucleophile takes the place of the leaving group on the carbonyl compound by way of an intermediate state that does not contain a carbonyl. Both steps are [[reversible reaction|reversible]] and as a result, nucleophilic acyl substitution reactions are equilibrium processes.<ref>Wade 2010, pp. 996–997.</ref>{{Full citation needed|date=June 2017}} Because the equilibrium will favor the product containing the best nucleophile, the leaving group must be a comparatively poor nucleophile in order for a reaction to be practical.

===Acidic conditions===
Under acidic conditions, the carbonyl group of the acyl compound '''1''' is protonated, which activates it towards nucleophilic attack. In the second step, the protonated carbonyl '''2''' is attacked by a nucleophile (H−Z) to give tetrahedral intermediate '''3'''. Proton transfer from the nucleophile (Z) to the leaving group (X) gives '''4''', which then collapses to eject the protonated leaving group (H−X), giving protonated carbonyl compound '''5'''. The loss of a proton gives the substitution product, '''6'''. Because the last step involves the loss of a proton, nucleophilic acyl substitution reactions are considered catalytic in acid. Also note that under acidic conditions, a nucleophile will typically exist in its protonated form (i.e. H−Z instead of Z<sup>−</sup>).

:[[File:General Scheme for Acid Catalyzed Nucleophilic Acyl Substitution.png|A general mechanism for acid catalyzed nucleophilic acyl substitution|800px]]

===Basic conditions===
Under [[base (chemistry)|basic]] conditions, a nucleophile (Nuc) attacks the carbonyl group of the acyl compound '''1''' to give tetrahedral alkoxide intermediate '''2'''. The intermediate collapses and expels the leaving group (X) to give the substitution product '''3'''. While nucleophilic acyl substitution reactions can be base-catalyzed, the reaction will not occur if the leaving group is a stronger base than the nucleophile (i.e. the leaving group must have a higher p''K''<sub>a</sub> than the nucleophile). Unlike acid-catalyzed processes, both the nucleophile and the leaving group exist as anions under basic conditions.

:[[File:General Scheme for Base Catalyzed Nucleophilc Acyl Substitution.png|A general mechanism for base catalyzed nucleophilic acyl substitution|400px]]

This mechanism is supported by [[isotope labeling]] experiments. When [[ethyl propionate]] with an [[oxygen-18]]-labeled ethoxy group is treated with [[sodium hydroxide]] (NaOH), the oxygen-18 label is completely absent from [[propionic acid]] and is found exclusively in the [[ethanol]].<ref name=mcmurry>{{cite book|last=McMurry|first=John|title=Organic Chemistry|year=1996|publisher=Brooks/Cole Publishing Company|location=Pacific Grove, CA|isbn=0534238327|pages=[https://archive.org/details/organicchemistry00mcmu/page/820 820–821]|edition=4th|url=https://archive.org/details/organicchemistry00mcmu/page/820}}</ref>

:[[File:Nucleophilic Acyl Substitution with a Labeled Oxygen.png|Reacting isotopically labeled ethyl propionate with sodium hydroxide proves the proposed mechanism for nucleophilic acyl substitution.|600px]]

==Acyl species==
In '''acyloxy''' groups the acyl group is bonded to oxygen: R−C(=O)−O−R′ where R−C(=O) is the acyl group.

[[Acylium ion]]s are [[cation]]s of the formula R−C≡O<sup>+</sup>. They are intermediates in [[Friedel-Crafts acylation]]s.

==See also==
*[[Acylation]]
*[[Functional group]]

==References==
{{reflist}}

==External links==
*{{Commons category-inline}}

{{Functional groups}}
{{Authority control}}

[[Category:Acyl groups| ]]
[[Category:Functional groups]]