Acyl chloride

Last updated
General chemical structure of an acyl chloride General structural formula of carboxylic acid chlorides.svg
General chemical structure of an acyl chloride

In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group −C(=O)Cl. Their formula is usually written R−COCl, where R is a side chain. They are reactive derivatives of carboxylic acids (R−C(=O)OH). A specific example of an acyl chloride is acetyl chloride, CH3COCl. Acyl chlorides are the most important subset of acyl halides.

Contents

Nomenclature

Where the acyl chloride moiety takes priority, acyl chlorides are named by taking the name of the parent carboxylic acid, and substituting -yl chloride for -ic acid. Thus:

acetic acid (CH3COOH) → acetyl chloride (CH3COCl)
benzoic acid (C6H5COOH) → benzoyl chloride (C6H5COCl)
butyric acid (C3H7COOH) → butyryl chloride (C3H7COCl)

(Idiosyncratically, for some trivial names, -oyl chloride substitutes -ic acid. For example, pivalic acid becomes pivaloyl chloride and acrylic acid becomes acryloyl chloride. The names pivalyl chloride and acrylyl chloride are less commonly used, although they are arguably more logical.)

When other functional groups take priority, acyl chlorides are considered prefixes — chlorocarbonyl-: [1]

acetic acid (CH3COOH) → (chlorocarbonyl)acetic acid (ClOCCH2COOH)

Properties

Lacking the ability to form hydrogen bonds, acyl chlorides have lower boiling and melting points than similar carboxylic acids. For example, acetic acid boils at 118 °C, whereas acetyl chloride boils at 51 °C. Like most carbonyl compounds, infrared spectroscopy reveals a band near 1750 cm−1.

The simplest stable acyl chloride is acetyl chloride; formyl chloride is not stable at room temperature, although it can be prepared at –60 °C or below. [2] [3]

Acyl chlorides hydrolyze (react with water) to form the corresponding carboxylic acid and hydrochloric acid:

Structure of 3,5-dinitrobenzoyl chloride with selected bond distances (picometers) and bond angles shown in red. Structure of 3,5-dinitrobenzoyl chloride.svg
Structure of 3,5-dinitrobenzoyl chloride with selected bond distances (picometers) and bond angles shown in red.

Synthesis

Industrial routes

The industrial route to acetyl chloride involves the reaction of acetic anhydride with hydrogen chloride: [5]

Propionyl chloride is produced by chlorination of propionic acid with phosgene: [6]

Benzoyl chloride is produced by the partial hydrolysis of benzotrichloride: [7]

Similarly, benzotrichlorides react with carboxylic acids to the acid chloride. This conversion is practiced for the reaction of 1,4-bis(trichloromethyl)benzene to give terephthaloyl chloride:

Laboratory methods: thionyl chloride

In the laboratory, acyl chlorides are generally prepared by treating carboxylic acids with thionyl chloride (SOCl2). [8] The reaction is catalyzed by dimethylformamide and other additives. [9] [10]

Formation of acyl chloride.svg

Thionyl chloride [11] ⁠ is a well-suited reagent as the by-products (HCl, SO2) are gases and residual thionyl chloride can be easily removed as a result of its low boiling point (76 °C).

Laboratory methods: phosphorus chlorides

Phosphorus trichloride (PCl3) is popular, [12] although excess reagent is required. [9] Phosphorus pentachloride (PCl5) is also effective, [13] [14] but only one chloride is transferred:

Laboratory methods: oxalyl chloride

Another method involves the use of oxalyl chloride:

The reaction is catalysed by dimethylformamide (DMF), which reacts with oxalyl chloride to give the Vilsmeier reagent, an iminium intermediate that which reacts with the carboxylic acid to form a mixed imino-anhydride. This structure undergoes an acyl substitution with the liberated chloride, forming the acid anhydride and releasing regenerated molecule of DMF. [10] Relative to thionyl chloride, oxalyl chloride is more expensive but also a milder reagent and therefore more selective.

Reaction to give acyl chloride and DMF.png

Other laboratory methods

Acid chlorides can be used as a chloride source. [15] Thus acetyl chloride can be distilled from a mixture of benzoyl chloride and acetic acid: [9]

Other methods that do not form HCl include the Appel reaction: [16]

Another is the use of cyanuric chloride: [17]

Reactions

Acyl chloride are reactive, versatile reagents. [18] Acyl chlorides have a greater reactivity than other carboxylic acid derivatives like acid anhydrides, esters or amides:

Acyl chloride reactivity comparison.svg

Nucleophilic reactions

Acid chlorides are useful for the preparation of amides, esters, anhydrides. These reactions generate chloride, which can be undesirable. Acyl chlorides hydrolyze, yielding the carboxylic acid:

Carbonsaurechlorid-Reaktion1-V1.svg

This hydrolysis is usually a nuisance rather than intentional. Acyl chlorides are used to prepare acid anhydrides, amides and esters, by reacting acid chlorides with: a salt of a carboxylic acid, an amine, or an alcohol, respectively.

Carbonsaurechlorid-Reaktion5-V1.svg
Carbonsaurechlorid-Reaktion2-V1.svg
Carbonsaurechlorid-Reaktion3-V1.svg

Mechanism

The alcoholysis of acyl halides (the alkoxy-dehalogenation) is believed to proceed via an SN2 mechanism (Scheme 10). [19] ⁠ However, the mechanism can also be tetrahedral or SN1 in highly polar solvents [20] ⁠ (while the SN2 reaction involves a concerted reaction, the tetrahedral addition-elimination pathway involves a discernible intermediate). [21]

Acyl chloride reaction reaction mechanism.svg

Bases, such as pyridine or N,N-dimethylformamide, catalyze acylations. [14] [10] These reagents activate the acyl chloride via a nucleophilic catalysis mechanism. The amine attacks the carbonyl bond and presumably [22] ⁠ first forms a transient tetrahedral intermediate, then forms a quaternary acylammonium salt by the displacement of the leaving group. This quaternary acylammonium salt is more susceptible to attack by alcohols or other nucleophiles.

Acyl chloride amine reaction mechanism.svg

The use of two phases (aqueous for amine, organic for acyl chloride) is called the Schotten-Baumann reaction. This approach is used in the preparation of nylon via the so-called nylon rope trick. [23] ⁠

Conversion to ketones

Carbon nucleophiles such as Grignard reagents, convert acyl chlorides to ketones, which in turn are susceptible to the attack by second equivalent to yield the tertiary alcohol. The reaction of acyl halides with certain organocadmium reagents stops at the ketone stage. [24] The reaction with Gilman reagents also afford ketones, reflecting the low nucleophilicity of these lithium diorganocopper compounds. [14]

Reduction

Acyl chlorides are reduced by lithium aluminium hydride and diisobutylaluminium hydride to give primary alcohols. Lithium tri-tert-butoxyaluminium hydride, a bulky hydride donor, reduces acyl chlorides to aldehydes, as does the Rosenmund reduction using hydrogen gas over a poisoned palladium catalyst. [25]

The Rosenmund reduction Rosenmund reduction scheme.svg
The Rosenmund reduction

Acylation of arenes

With Lewis acid catalysts like ferric chloride or aluminium chloride, acyl chlorides participate in Friedel-Crafts acylations, to give aryl ketones: [12] [14]

F-C acylation mechanism.png

Because of the harsh conditions and the reactivity of the intermediates, this otherwise quite useful reaction tends to be messy, as well as environmentally unfriendly.

Oxidative addition

Acyl chlorides react with low-valent metal centers to give transition metal acyl complexes. Illustrative is the oxidative addition of acetyl chloride to Vaska's complex, converting square planar Ir(I) to octahedral Ir(III): [26]

Hazards

Low molecular weight acyl chlorides are often lachrymators, and they react violently with water, alcohols, and amines.

Related Research Articles

<span class="mw-page-title-main">Carboxylic acid</span> Organic compound containing a –C(=O)OH group

In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group attached to an R-group. The general formula of a carboxylic acid is often written as R−COOH or R−CO2H, sometimes as R−C(O)OH with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic acids occur widely. Important examples include the amino acids and fatty acids. Deprotonation of a carboxylic acid gives a carboxylate anion.

<span class="mw-page-title-main">Ketene</span> Organic compound of the form >C=C=O

In organic chemistry, a ketene is an organic compound of the form RR'C=C=O, where R and R' are two arbitrary monovalent chemical groups. The name may also refer to the specific compound ethenone H2C=C=O, the simplest ketene.

<span class="mw-page-title-main">Thioester</span> Organosulfur compounds of the form R–SC(=O)–R’

In organic chemistry, thioesters are organosulfur compounds with the molecular structure R−C(=O)−S−R’. They are analogous to carboxylate esters with the sulfur in the thioester replacing oxygen in the carboxylate ester, as implied by the thio- prefix. They are the product of esterification of a carboxylic acid with a thiol. In biochemistry, the best-known thioesters are derivatives of coenzyme A, e.g., acetyl-CoA. The R and R' represent organyl groups, or H in the case of R.

<span class="mw-page-title-main">Fischer–Speier esterification</span>

Fischer esterification or Fischer–Speier esterification is a special type of esterification by refluxing a carboxylic acid and an alcohol in the presence of an acid catalyst. The reaction was first described by Emil Fischer and Arthur Speier in 1895. Most carboxylic acids are suitable for the reaction, but the alcohol should generally be primary or secondary. Tertiary alcohols are prone to elimination. Contrary to common misconception found in organic chemistry textbooks, phenols can also be esterified to give good to near quantitative yield of products. Commonly used catalysts for a Fischer esterification include sulfuric acid, p-toluenesulfonic acid, and Lewis acids such as scandium(III) triflate. For more valuable or sensitive substrates other, milder procedures such as Steglich esterification are used. The reaction is often carried out without a solvent or in a non-polar solvent to facilitate the Dean-Stark method. Typical reaction times vary from 1–10 hours at temperatures of 60-110 °C.

In chemistry, acylation is a broad class of chemical reactions in which an acyl group is added to a substrate. The compound providing the acyl group is called the acylating agent. The substrate to be acylated and the product include the following:

<span class="mw-page-title-main">Acyl halide</span> Oxoacid compound with an –OH group replaced by a halogen

In organic chemistry, an acyl halide is a chemical compound derived from an oxoacid by replacing a hydroxyl group with a halide group.

In chemistry, acetylation is an organic esterification reaction with acetic acid. It introduces an acetyl group into a chemical compound. Such compounds are termed acetate esters or simply acetates. Deacetylation is the opposite reaction, the removal of an acetyl group from a chemical compound.

<span class="mw-page-title-main">Acetyl chloride</span> Organic compound (CH₃COCl)

Acetyl chloride is an acyl chloride derived from acetic acid. It belongs to the class of organic compounds called acid halides. It is a colorless, corrosive, volatile liquid. Its formula is commonly abbreviated to AcCl.

<span class="mw-page-title-main">Sulfonic acid</span> Organic compounds with the structure R−S(=O)2−OH

In organic chemistry, sulfonic acid refers to a member of the class of organosulfur compounds with the general formula R−S(=O)2−OH, where R is an organic alkyl or aryl group and the S(=O)2(OH) group a sulfonyl hydroxide. As a substituent, it is known as a sulfo group. A sulfonic acid can be thought of as sulfuric acid with one hydroxyl group replaced by an organic substituent. The parent compound is the parent sulfonic acid, HS(=O)2(OH), a tautomer of sulfurous acid, S(=O)(OH)2. Salts or esters of sulfonic acids are called sulfonates.

<span class="mw-page-title-main">Oxalyl chloride</span> Chemical compound

Oxalyl chloride is an organic chemical compound with the formula Cl−C(=O)−C(=O)−Cl. This colorless, sharp-smelling liquid, the diacyl chloride of oxalic acid, is a useful reagent in organic synthesis.

<span class="mw-page-title-main">Thionyl chloride</span> Inorganic compound (SOCl2)

Thionyl chloride is an inorganic compound with the chemical formula SOCl2. It is a moderately volatile, colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a chlorinating reagent, with approximately 45,000 tonnes per year being produced during the early 1990s, but is occasionally also used as a solvent. It is toxic, reacts with water, and is also listed under the Chemical Weapons Convention as it may be used for the production of chemical weapons.

<span class="mw-page-title-main">Organic acid anhydride</span> Any chemical compound having two acyl groups bonded to the same oxygen atom

An organic acid anhydride is an acid anhydride that is also an organic compound. An acid anhydride is a compound that has two acyl groups bonded to the same oxygen atom. A common type of organic acid anhydride is a carboxylic anhydride, where the parent acid is a carboxylic acid, the formula of the anhydride being (RC(O))2O. Symmetrical acid anhydrides of this type are named by replacing the word acid in the name of the parent carboxylic acid by the word anhydride. Thus, (CH3CO)2O is called acetic anhydride.Mixed (or unsymmetrical) acid anhydrides, such as acetic formic anhydride (see below), are known, whereby reaction occurs between two different carboxylic acids. Nomenclature of unsymmetrical acid anhydrides list the names of both of the reacted carboxylic acids before the word "anhydride" (for example, the dehydration reaction between benzoic acid and propanoic acid would yield "benzoic propanoic anhydride").

Nucleophilic acyl substitution describes a class of substitution reactions involving nucleophiles and acyl compounds. In this type of reaction, a nucleophile – such as an alcohol, amine, or enolate – displaces the leaving group of an acyl derivative – such as an acid halide, anhydride, or ester. The resulting product is a carbonyl-containing compound in which the nucleophile has taken the place of the leaving group present in the original acyl derivative. Because acyl derivatives react with a wide variety of nucleophiles, and because the product can depend on the particular type of acyl derivative and nucleophile involved, nucleophilic acyl substitution reactions can be used to synthesize a variety of different products.

<span class="mw-page-title-main">Trimethylsilyl chloride</span> Organosilicon compound with the formula (CH3)3SiCl

Trimethylsilyl chloride, also known as chlorotrimethylsilane is an organosilicon compound, with the formula (CH3)3SiCl, often abbreviated Me3SiCl or TMSCl. It is a colourless volatile liquid that is stable in the absence of water. It is widely used in organic chemistry.

<span class="mw-page-title-main">Triflic acid</span> Chemical compound

Triflic acid, the short name for trifluoromethanesulfonic acid, TFMS, TFSA, HOTf or TfOH, is a sulfonic acid with the chemical formula CF3SO3H. It is one of the strongest known acids. Triflic acid is mainly used in research as a catalyst for esterification. It is a hygroscopic, colorless, slightly viscous liquid and is soluble in polar solvents.

In organic chemistry, the acetoxy group, is a functional group with the formula −OCOCH3 and the structure −O−C(=O)−CH3. As the -oxy suffix implies, it differs from the acetyl group by the presence of an additional oxygen atom. The name acetoxy is the short form of acetyl-oxy.

<span class="mw-page-title-main">Disodium tetracarbonylferrate</span> Chemical compound

Disodium tetracarbonylferrate is the organoiron compound with the formula Na2[Fe(CO)4]. It is always used as a solvate, e.g., with tetrahydrofuran or dimethoxyethane, which bind to the sodium cation. An oxygen-sensitive colourless solid, it is a reagent in organometallic and organic chemical research. The dioxane solvated sodium salt is known as Collman's reagent, in recognition of James P. Collman, an early popularizer of its use.

Acetyl iodide is an organoiodine compound with the formula CH3COI. It is a colourless liquid. It is formally derived from acetic acid. Although far rarer in the laboratory than the related acetyl bromide and acetyl chloride, acetyl iodide is produced, transiently at least, on a far larger scale than any other acid halide. Specifically, it is generated by the carbonylation of methyl iodide in the Cativa and Monsanto processes, which are the main industrial processes that generate acetic acid. It is also an intermediate in the production of acetic anhydride from methyl acetate.

An insertion reaction is a chemical reaction where one chemical entity interposes itself into an existing bond of typically a second chemical entity e.g.:

<span class="mw-page-title-main">Acetyl hypochlorite</span> Chemical compound

Acetyl hypochlorite, also known as chlorine acetate, is a chemical compound with the formula CH3COOCl. It is a photosensitive colorless liquid that is a short lived intermediate in the Hunsdiecker reaction.

References

  1. ↑ Nomenclature of Organic Chemistry, R-5.7.6 Acid halides
  2. ↑ Sih, John C. (2001-04-15), "Formyl Chloride", in John Wiley & Sons, Ltd (ed.), Encyclopedia of Reagents for Organic Synthesis, John Wiley & Sons, Ltd, doi:10.1002/047084289x.rf026, ISBN   9780471936237
  3. ↑ Richard O.C. Norman; James M. Coxon (16 September 1993). Principles of Organic Synthesis, 3rd Edition. CRC Press. p. 371. ISBN   978-0-7487-6162-3.
  4. ↑ Wang, Hong-Yong; Xie, Min-Hao; Luo, Shi-Neng; Zou, Pei; Liu, Ya-Ling (2009). "3,5-Dinitrobenzoyl chloride". Acta Crystallographica Section E. 65 (10): o2460. doi:10.1107/S1600536809036228. PMC   2970283 . PMID   21577915.
  5. ↑ USpatent 5672749,Phillip R. DeVrou, W. Bryan Waites, Robert E. Young,"Process for preparing acetyl chloride"
  6. ↑ Samel, Ulf-Rainer; Kohler, Walter; Gamer, Armin Otto; Keuser, Ullrich (2005). "Propionic acid and derivatives". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a22_223. ISBN   978-3527306732.
  7. ↑ Maki, Takao; Takeda, Kazuo (2002). "Benzoic acid and derivatives". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a03_555. ISBN   978-3527306732.
  8. ↑ Helferich, B.; Schaefer, W. (1929). "n-Butyrl chloride". Organic Syntheses. 9: 32. doi:10.15227/orgsyn.009.0032.
  9. 1 2 3 Martin Ansell (1972). "Preparation of acyl halides". In Saul Patai (ed.). Acyl Halides. PATAI'S Chemistry of Functional Groups. pp. 35–68. doi:10.1002/9780470771273.ch2. ISBN   9780470771273.
  10. 1 2 3 Clayden, Jonathan (2001). Organic chemistry . Oxford: Oxford University Press. pp.  276–296. ISBN   0-19-850346-6.
  11. ↑ J. S. Pizey, Synthetic Reagents, Vol. 1, Halsted Press, New York, 1974.
  12. 1 2 Allen, C. F. H.; Barker, W. E. (1932). "Desoxybenzoin". Organic Syntheses. 12: 16. doi:10.15227/orgsyn.012.0016.
  13. ↑ Adams, Roger (1923). "p-Nitrobenzoyl Chloride". Organic Syntheses. 3: 75. doi:10.15227/orgsyn.003.0075.
  14. 1 2 3 4 Boyd, Robert W.; Morrison, Robert (1992). Organic Chemistry. Englewood Cliffs, N.J: Prentice Hall. pp. 666–762. ISBN   0-13-643669-2.
  15. ↑ L. P. Kyrides (1940). "Fumaryl Chloride". Organic Syntheses. 20: 51. doi:10.15227/orgsyn.020.0051.
  16. ↑ "Triphenylphosphine-carbon tetrachloride Taschner, Michael J. e-EROS: Encyclopedia of Reagents for Organic Synthesis, 2001
  17. ↑ K. Venkataraman; D. R. Wagle (1979). "Cyanuric chloride : a useful reagent for converting carboxylic acids into chlorides, esters, amides and peptides". Tetrahedron Lett. 20 (32): 3037–3040. doi:10.1016/S0040-4039(00)71006-9.
  18. ↑ Sonntag, Norman O. V. (1953-04-01). "The Reactions of Aliphatic Acid Chlorides". Chemical Reviews. 52 (2): 237–416. doi:10.1021/cr60162a001. ISSN   0009-2665.
  19. ↑ Bentley, T. William; Llewellyn, Gareth; McAlister, J. Anthony (January 1996). "SN2 Mechanism for Alcoholysis, Aminolysis, and Hydrolysis of Acetyl Chloride". The Journal of Organic Chemistry. 61 (22): 7927–7932. doi:10.1021/jo9609844. ISSN   0022-3263. PMID   11667754.
  20. ↑ C. H. Bamford and C. F. H. Tipper, Comprehensive Chemical Kinetics: Ester Formation and Hydrolysis and Related Reactions, Elsevier, Amsterdam, 1972.
  21. ↑ Fox, Joseph M.; Dmitrenko, Olga; Liao, Lian-an; Bach, Robert D. (October 2004). "Computational Studies of Nucleophilic Substitution at Carbonyl Carbon: the S N 2 Mechanism versus the Tetrahedral Intermediate in Organic Synthesis". The Journal of Organic Chemistry. 69 (21): 7317–7328. doi:10.1021/jo049494z. ISSN   0022-3263. PMID   15471486.
  22. ↑ Hubbard, Patricia; Brittain, William J. (February 1998). "Mechanism of Amine-Catalyzed Ester Formation from an Acid Chloride and Alcohol". The Journal of Organic Chemistry. 63 (3): 677–683. doi:10.1021/jo9716643. ISSN   0022-3263. PMID   11672060.
  23. ↑ Morgan, Paul W.; Kwolek, Stephanie L. (April 1959). "The nylon rope trick: Demonstration of condensation polymerization". Journal of Chemical Education. 36 (4): 182. Bibcode:1959JChEd..36..182M. doi:10.1021/ed036p182. ISSN   0021-9584.
  24. ↑ David A. Shirley (2011). "The Synthesis of Ketones from Acid Halides and Organometallic Compounds of Magnesium, Zinc, and Cadmium". Org. Reactions: 28–58. doi:10.1002/0471264180.or008.02. ISBN   978-0471264187.
  25. ↑ William Reusch. "Carboxylic Acid Derivatives". VirtualText of Organic Chemistry. Michigan State University. Archived from the original on 2016-05-16. Retrieved 2009-02-19.
  26. ↑ Hartwig, John (2010). Organotransition Metal Chemistry: From Bonding to Catalysis. New York: University Science Books. p. 1160. ISBN   978-1-938787-15-7.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.