Acyl group

Inchemistry,anacyl groupis amoietyderived by the removal of one or morehydroxylgroups from anoxoacid,includinginorganic acids.It contains a double-bondedoxygenatomand anorganyl group(R−C=O) orhydrogenin the case offormyl group(H−C=O). Inorganic chemistry,the acyl group (IUPACnamealkanoylif the organyl group isalkyl) is usually derived from acarboxylic acid,in which case it has the formulaR−C(=O)−,where R represents anorganylgroup orhydrogen.Although the term is almost always applied to organic compounds, acyl groups can in principle be derived from other types of acids such assulfonic acidsandphosphonic acids.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 adouble bond.

A general acyl group (blue) in aketone(top left), as an acyliumcation(top centre), as an acylradical(top right), analdehyde(bottom left),ester(bottom centre) oramide(bottom right). (R¹,R²and R³stands fororganylsubstituent orhydrogenin the case ofR¹)

Reactivity trends

There are five main types of acyl derivatives.Acid halidesare the most reactive towards nucleophiles, followed byanhydrides,esters,andamides.Carboxylateions 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 10¹³.

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 strongconjugate acid(e.g.hydrochloric acid) will be a better leaving group than a species with a weak conjugate acid (e.g.acetic acid). Thus,chlorideion is a better leaving group thanacetate ion.The reactivity of acyl compounds towards nucleophiles decreases as the basicity of the leaving group increases, as the table shows.

Compound Name	Structure	Leaving Group	pKaof Conjugate Acid
Acetyl chloride			−7
Acetic anhydride			4.76
Ethyl acetate			15.9
Acetamide			38
Acetateanion		N/a	N/a

The two major resonance forms of an amide.

Another factor that plays a role in determining the reactivity of acyl compounds isresonance.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 significantdouble bondcharacter. Theenergy barrierfor 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).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.

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.

Compounds

Well-known acyl compounds are theacyl chlorides,such asacetyl chloride(CH₃COCl) andbenzoyl chloride(C₆H₅COCl). These compounds, which are treated as sources of acylium cations, are goodreagentsfor attaching acyl groups to various substrates.Amides(RC(O)NR′₂) andesters(RC(O)OR′) are classes of acyl compounds, as areketones(RC(O)R′) andaldehydes(RC(O)H), where R and R′ stand fororganyl(orhydrogenin the case offormyl).

Acylium cations, radicals, and anions

Resonance structures of acylium ion

Acylium ions arecationsof the formulaRCO⁺.The carbon–oxygenbond lengthin these cations is near 1.1Å(110-112 pm), which is shorter than the 112.8 pm ofcarbon monoxideand indicatestriple-bondcharacter.

The carbon centres of acylium ions generally have alinear geometryand spatomic hybridization,and are best represented by aresonance structurebearing a formal positive charge on the oxygen (rather than carbon):[R−C≡O⁺].They are characteristic fragments observed in EI-mass spectraofketones.

Acylium ions are common reactive intermediates, for example in theFriedel–Crafts acylationand many otherorganic reactionssuch as theHayashi rearrangement.Salts containing acylium ions can be generated by removal of the halide fromacyl halides:

RC(O)Cl + SbCl₅→ [RCO]⁺[SbCl₆]⁻

Acylradicalsare readily generated from aldehydes by hydrogen-atom abstraction. However, they undergo rapiddecarbonylationto afford the alkyl radical:

RC(H)=O → RC^•=O → R^•+ C≡O

Acylanionsare almost always unstable—usually too unstable to be exploited synthetically. They readily react with the neutral aldehyde to form anacyloindimer. Hence, synthetic chemists have developed various acyl anionsynthetic equivalents,such asdithianes,as surrogates. However, as a partial exception, hindered dialkylformamides (e.g., diisopropylformamide, HCONiPr₂) can undergo deprotonation at low temperature (−78 °C) withlithium diisopropylamideas the base to form acarbamoylanion stable at these temperatures.

In biochemistry

Inbiochemistrythere are many instances of acyl groups, in all major categories of biochemical molecules.

Acyl-CoAsare acyl derivatives formed viafatty acidmetabolism.Acetyl-CoA,the most common derivative, serves as an acyl donor in many biosynthetic transformations. Such acyl compounds arethioesters.

Names of acyl groups ofamino acidsare formed by replacing the-inesuffix with-yl.For example, the acyl group ofglycineisglycyl,and oflysineislysyl.

Names of acyl groups ofribonucleoside monophosphatessuch asAMP(5′-adenylic acid),GMP(5′-guanylic acid),CMP(5′-cytidylic acid), andUMP(5′-uridylic acid) are adenylyl, guanylyl, cytidylyl, and uridylyl respectively.

Inphospholipids,the acyl group ofphosphatidic acidis called phosphatidyl-.

Finally, manysaccharidesare acylated.

In organometallic chemistry and catalysis

Main article:Transition metal acyl complexes

Acylligandsare intermediates in manycarbonylationreactions, which are important in some catalytic reactions. Metal acyls arise usually via insertion ofcarbon monoxideinto metal–alkylbonds. 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 thebasicityof the oxygen center.O-alkylation of metal acyls givesFischer carbenecomplexes.

Nomenclature

Thecommon namesof acyl groups are derived typically by replacing the-ic acidsuffix of the correspondingcarboxylic acid's common name with-yl(or-oyl), as shown in the table below.

In theIUPAC nomenclature of organic chemistry,thesystematic namesof acyl groups are derived exactly by replacing the-ylsuffix of the correspondinghydrocarbylgroup's systemic name (or the-oic acidsuffix of the correspondingcarboxylic acid's systemic name) with-oyl,as shown in the table below.

The acyls are between the hydrocarbyls and the carboxylic acids.

Thehydrocarbylgroup names that end in -yl are not acyl groups, butalkylgroups derived fromalkanes(methyl,ethyl,propyl,butyl), alkenyl groups derived fromalkenes(propenyl,butenyl), orarylgroups (benzyl).

Correspondinghydrocarbylgroup name RC–		Acyl group name RC(O)–		Correspondingcarboxylic acidname RC(O)O-H
common	systematic	common	systematic	common	systematic
methyl		formyl	methanoyl	formicacid	methanoicacid
ethyl		acetyl	ethanoyl	aceticacid	ethanoicacid
propyl		propionyl	propanoyl	propionicacid	propanoicacid
butyl		butyryl	butanoyl	butyricacid	butanoicacid
propenyl		acrylyloracryloyl	propenoyl	acrylicacid	propenoicacid
crotyl	butenyl	crotonyl	butenoyl	crotonicacid	butenoicacid
benzyl		benzoyl		benzoicacid

Reaction mechanisms

Acyl compounds react with nucleophiles via an addition mechanism: the nucleophile attacks the carbonyl carbon, forming atetrahedral intermediate.This reaction can be accelerated byacidicconditions, which make the carbonyl moreelectrophilic,orbasicconditions, which provide a moreanionicand therefore more reactive nucleophile. The tetrahedral intermediate itself can be an alcohol oralkoxide,depending on thepHof the reaction.

The tetrahedral intermediate of anacylcompound contains asubstituentattached to the central carbon that can act as aleaving group.After the tetrahedral intermediate forms, it collapses, recreating the carbonyl C=O bond and ejecting the leaving group in anelimination 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 arereversibleand as a result, nucleophilic acyl substitution reactions are equilibrium processes.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 compound1is protonated, which activates it towards nucleophilic attack. In the second step, the protonated carbonyl2is attacked by a nucleophile (H−Z) to give tetrahedral intermediate3.Proton transfer from the nucleophile (Z) to the leaving group (X) gives4,which then collapses to eject the protonated leaving group (H−X), giving protonated carbonyl compound5.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⁻).

Basic conditions

Underbasicconditions, a nucleophile (Nuc) attacks the carbonyl group of the acyl compound1to give tetrahedral alkoxide intermediate2.The intermediate collapses and expels the leaving group (X) to give the substitution product3.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 pK_athan the nucleophile). Unlike acid-catalyzed processes, both the nucleophile and the leaving group exist as anions under basic conditions.

This mechanism is supported byisotope labelingexperiments. Whenethyl propionatewith anoxygen-18-labeled ethoxy group is treated withsodium hydroxide(NaOH), the oxygen-18 label is completely absent frompropionic acidand is found exclusively in theethanol.

Acyl species

Inacyloxygroups the acyl group is bonded to oxygen: R−C(=O)−O−R′ where R−C(=O) is the acyl group.

Acylium ionsarecationsof the formula R−C≡O⁺.They are intermediates inFriedel-Crafts acylations.

See also

• Acylation
• Functional group

External links

• Media related toAcyl groupsat Wikimedia Commons