Inchemistry, anacyl group is amoiety derived by the removal of one or morehydroxyl groups from anoxoacid,[1] includinginorganic acids. It contains a double-bondedoxygenatom and anorganyl group (R−C=O) orhydrogen in the case offormyl group (H−C=O). Inorganic chemistry, the acyl group (IUPAC namealkanoyl if the organyl group isalkyl) is usually derived from acarboxylic acid, in which case it has the formulaR−C(=O)−, where R represents anorganyl group 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 acids andphosphonic 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.
There are five main types of acyl derivatives.Acid halides are the most reactive towards nucleophiles, followed byanhydrides,esters, andamides.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 1013.[2]
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,chloride ion 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.[3]
| Compound Name | Structure | Leaving Group | pKa of Conjugate Acid |
|---|---|---|---|
| Acetyl chloride |  |  | −7 |
| Acetic anhydride |  |  | 4.76 |
| Ethyl acetate |  |  | 15.9 |
| Acetamide |  |  | 38 |
| Acetate anion | | N/a | N/a |
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 bond character. Theenergy 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).[2] 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.[3]
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.[3]
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 goodreagents for 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 (orhydrogen in the case offormyl).
Acylium ions arecations of the formulaRCO+.[4] The carbon–oxygenbond length in these cations is near 1.1 Å (110-112 pm), which is shorter than the 112.8 pm ofcarbon monoxide and indicatestriple-bond character.[5][6][7]
The carbon centres of acylium ions generally have alinear geometry and spatomic hybridization, and are best represented by aresonance structure bearing a formal positive charge on the oxygen (rather than carbon):[R−C≡O+]. They are characteristic fragments observed in EI-mass spectra ofketones.
Acylium ions are common reactive intermediates, for example in theFriedel–Crafts acylation and many otherorganic reactions such as theHayashi rearrangement. Salts containing acylium ions can be generated by removal of the halide fromacyl halides:
Acylradicals are commonly generated whenthiyl or other, more electrophilic radicals abstract hydrogen atoms fromaldehydes (alkyl radicals do so very inefficiently). However, they undergo rapid, reversible[8]decarbonylation to afford the alkyl radical:[9]
Acylanions are almost always unstable—usually too unstable to be exploited synthetically. They readily react with the neutral aldehyde to form anacyloin dimer. 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 diisopropylamide as the base to form acarbamoyl anion stable at these temperatures.[10]
Inbiochemistry there are many instances of acyl groups, in all major categories of biochemical molecules.
Acyl-CoAs are acyl derivatives formed viafatty acid metabolism.Acetyl-CoA, the most common derivative, serves as an acyl donor in many biosynthetic transformations. Such acyl compounds arethioesters.
Names of acyl groups ofamino acids are formed by replacing the-ine suffix with-yl. For example, the acyl group ofglycine isglycyl, and oflysine islysyl.
Names of acyl groups ofribonucleoside monophosphates such 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 acid is called phosphatidyl-.
Finally, manysaccharides are acylated.
Acylligands are intermediates in manycarbonylation reactions, which are important in some catalytic reactions. Metal acyls arise usually via insertion ofcarbon 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 thebasicity of the oxygen center.O-alkylation of metal acyls givesFischer carbene complexes.[11]
Thecommon names of acyl groups are derived typically by replacing the-ic acid suffix of the correspondingcarboxylic acid's common name with-yl (or-oyl), as shown in the table below.
In theIUPAC nomenclature of organic chemistry, thesystematic names of acyl groups are derived exactly by replacing the-yl suffix of the correspondinghydrocarbyl group's systemic name (or the-oic acid suffix 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.
Thehydrocarbyl group names that end in -yl are not acyl groups, butalkyl groups derived fromalkanes (methyl,ethyl,propyl,butyl), alkenyl groups derived fromalkenes (propenyl, butenyl), oraryl groups (benzyl).
| Correspondinghydrocarbyl group name RC– | Acyl group name RC(O)– | Correspondingcarboxylic acid name RC(O)O-H | |||
|---|---|---|---|---|---|
| common | systematic | common | systematic | common | systematic |
| methyl | methanyl | formyl | methanoyl | formic acid | methanoic acid |
| ethyl | ethanyl | acetyl | ethanoyl | acetic acid | ethanoic acid |
| propyl | propanyl | propionyl | propanoyl | propionic acid | propanoic acid |
| butyl | butanyl | butyryl | butanoyl | butyric acid | butanoic acid |
| propenyl | acrylyl oracryloyl | propenoyl | acrylic acid | propenoic acid | |
| crotyl | butenyl | crotonyl | butenoyl | crotonic acid | butenoic acid |
| benzyl | benzoyl | benzoic acid | |||
Acyl compounds react with nucleophiles via an addition mechanism: the nucleophile attacks the carbonyl carbon, forming atetrahedral intermediate. This reaction can be accelerated byacidic conditions, which make the carbonyl moreelectrophilic, orbasic conditions, which provide a moreanionic and therefore more reactive nucleophile. The tetrahedral intermediate itself can be an alcohol oralkoxide, depending on thepH of the reaction.
The tetrahedral intermediate of anacyl compound contains asubstituent attached 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 arereversible and as a result, nucleophilic acyl substitution reactions are equilibrium processes.[12][full citation needed] 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.
Under acidic conditions, the carbonyl group of the acyl compound1 is protonated, which activates it towards nucleophilic attack. In the second step, the protonated carbonyl2 is 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−).
Underbasic conditions, a nucleophile (Nuc) attacks the carbonyl group of the acyl compound1 to 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 lower pKa than the nucleophile). Unlike acid-catalyzed processes, both the nucleophile and the leaving group exist as anions under basic conditions.
This mechanism is supported byisotope labeling experiments. Whenethyl propionate with anoxygen-18-labeled ethoxy group is treated withsodium hydroxide (NaOH), the oxygen-18 label is completely absent frompropionic acid and is found exclusively in theethanol.[13]
Inacyloxy groups the acyl group is bonded to oxygen: R−C(=O)−O−R′ where R−C(=O) is the acyl group.
Acylium ions arecations of the formula R−C≡O+. They are intermediates inFriedel-Crafts acylations.
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