Acylation

8 Key excerpts on "Acylation"

• 

  eBook - ePub

  DAT Prep Plus 2023-2024

  2 Practice Tests + Proven Strategies + Online

  • (Author)
  • 2023(Publication Date)
  • Kaplan Test Prep

    (Publisher)

  2 O as the nucleophile). They also undergo other additions and substitutions, including various interconversions between different acid derivatives. In general, the acyl halides are the most reactive of the carboxylic acid derivatives, followed by the anhydrides, the esters, and the amides.

  Each of these types of carboxylic acid derivatives will be discussed in turn. Although the variety of reaction pathways can appear overwhelming, they are all closely interwoven and should be studied in relation to each other. To aid your studies, a summary of the different reactions of carboxylic acid derivatives is included at the end of this chapter.

  Acyl Halides

  Nomenclature of Acyl Halides

  Acyl halides are also called acid or alkanoyl halides. The acyl group is written RCO–, and with the halide attached it is written as RCOX. Acyl halides are the most reactive of the carboxylic acid derivatives. They are named in the IUPAC system by changing the -ic acid ending of the carboxylic acid to -yl halide. Some typical examples are ethanoyl chloride (also called acetyl chloride), benzoyl chloride, and n-butanoyl bromide.

  Figure 48.1

  Properties of Acyl Halides

  Because the -OH of the carboxyl group has been replaced by a halogen, an acyl halide is not able to form hydrogen bonds. Acyl halides are therefore less polar than comparable carboxylic acids, and demonstrate significantly lower melting and boiling points. For example, acetyl chloride boils at 51°C, compared to acetic acid which boils at 118°C.

  Synthesis of Acyl Halides

  The most common acyl halides are the acid chlorides, although acid bromides and iodides are occasionally encountered. Acyl chlorides are prepared by reaction of a carboxylic acid with thionyl chloride, SOCl2 , producing SO2 and HCl as side products. Alternatively, PCl3 or PCl5 (or PBr3

  Sign up to read

  Learn more about book
• 

  eBook - PDF

  Advances in Friedel-Crafts Acylation Reactions

  Catalytic and Green Processes

  • Giovanni Sartori, Raimondo Maggi(Authors)
  • 2009(Publication Date)
  • CRC Press

    (Publisher)

  9 2 chapter Stoichiometric Acylations The classical Friedel–Crafts Acylation reactions are usually carried out in the presence of a stoichio‑ metric amount of Lewis acid catalyst and are very familiar today to all chemical research workers. In this chapter, only special examples of stoichio‑ metric Acylation will be commented. For example, reactions showing extraordinary level of regiose‑ lectivity promoted by proximity or metal template effects are described. Moreover, examples of effi‑ cient use of carboxylic acids and esters as acylating agents under soft experimental conditions in com‑ bination with ecocompatible solvents are stressed as new and practicable synthetic methods. Studies on the highly efficient multistep synthesis of polyfunc‑ tional compounds via bis‑Acylation and alkylation– Acylation processes are commented upon, and some mechanistic details are also shown. 2.1 Acylation The proximity effect of acyl groups covalently bounded to heteroaromatic compounds is advantageously exploited in the intramolecular regioselec‑ tive electrophilic Acylation of N‑substituted pyrroles (Scheme 2.1). 1 N -methylmorpholine, Et 2 O, 25°C, 1 h R = Me, Pr, Bu t , CH 2 Bu t N Me H COOH + RCOCl N Me H O O R O AlCl 3 , Et 2 O, 25°C, 17 h 65–81% N Me H COOH R O 1 2 3 Scheme 2.1 10 Advances in Friedel–Crafts Acylation reactions Thus, compound 1 , easily synthesized from proline and 2,6‑dimeth‑ oxytetrahydrofuran by the modified Clauson–Kaas procedure, 2 is con‑ verted into the mixed anhydrides 2 by reaction with different acyl chlorides and N ‑methylmorpholine. Treatment of compounds 2 with a stoichiometric amount of aluminum chloride in dry diethyl ether gives the C‑2 derivatives 3 in 65%–81% yield via intramolecular acyl transfer controlled by the proximity effect. Trace amounts of 3‑acyl derivatives are also produced by conventional intermolecular Acylation from another molecule of mixed anhydride 2 .

  Sign up to read

  Learn more about book
• 

  eBook - PDF

  Chemical Reagents for Protein Modification

  • Roger L. Lundblad(Author)
  • 2014(Publication Date)
  • CRC Press

    (Publisher)

  97 3 Acylating Agents The Acylation of amino acids involves the transfer of an acyl group (carbonyl group attached to an alkyl or aryl group) from an active donor such as a carboxylic acid anhydride (e.g., acetic anhydride), a carboxylic acid halide (e.g., acetyl chloride), or an active ester such as p -nitrophenyl acetate or N -hydroxysuccinimidyl acetate. This reaction can be described as nucleophilic acyl addition involving the carbonyl carbon. This mechanism is also used in the N -myristoylation of proteins. 1 Other acylating agents include N -acetylimidazole, 2-(acetoxy)-benzoic acid (aspirin), and the thioesters. The Acylation of the ε -amino group of lysine or the α -amino group is stable under physiological conditions of temperature and pH, while the Acylation of tyrosine can be reversed by base or hydroxylamine. The Acylation of an amino group forms a peptide/isopeptide bond which is cleaved under conditions of acid hydrolysis used for the preparation of amino acid analysis. Acylation can also occur at the serine hydroxyl, threonine hydroxyl, the thiol group of cysteine, and the imidazole ring of histidine. The stability of these modifications is variable. The Acylation of cysteine in proteins by palmitic acid that can occur by both enzymatic and nonenzymatic pathways 2,3 can yield relatively stable products that are reversed in vivo by protein thioesterases. 3,4 Acylation of the indole ring of tryptophan by acetic anhydride or acetyl chloride is accomplished in anhydrous trifluoroacetic acid. 5 I could not find evidence for the Acylation of the indole ring of tryptophan in proteins. The acetylation of the guanidino nitrogen of arginine was accomplished with octanoic acid in fuming sulfuric acid (oleum)* at 60°C. 6 Aldehydes and ketones differ from other carbonyl compounds such as acetyl chloride or acetic anhydride in that these compounds do not have a leaving group.

  Sign up to read

  Learn more about book
• 

  eBook - ePub

  Hydrocarbon Chemistry

  • George A. Olah, Arpad Molnar, G. K. Surya Prakash(Authors)
  • 2017(Publication Date)
  • Wiley

    (Publisher)

  8 Acylation

  The Acylation of aromatic hydrocarbons was first described by Friedel and Crafts in 1877.1 Since then the reaction has been widely and thoroughly studied. It is one of the most important reactions in synthetic organic chemistry and a widely applied method to prepare aromatic ketones. It is also of considerable practical significance in the chemical industry2 since the products are intermediates in the manufacture of fine chemicals and other intermediates. Related topics, which include the Hueben–Hoesch reaction and aldehyde synthesis (formylation of aromatics), and the Acylation of aliphatic compounds, in contrast, are less important, and consequently, will be treated accordingly. The Acylation of aromatic2 – 10 and aliphatic compounds10–13 and the related processes10,14–18 are covered in reviews, and discussions of Acylations can be found in other review papers about the use of homogeneous and heterogeneous electrophilic catalysts.19,20

  8.1 Acylation of Aromatics

  8.1.1 General Characteristics

  Friedel–Crafts Acylation is an electrophilic aromatic substitution to afford ketones by replacing one of the hydrogens of an aromatic ring. Carboxylic acid derivatives, characteristically acid halides and anhydrides, serve as acylating agents, and Lewis acid metal halides are the characteristic catalysts required to induce the transformation. Esters, in general, are not satisfactory reagents since they give both alkyl- and acyl-substituted products.

  In Friedel–Crafts Acylation of aromatics with acid chlorides and Lewis acid metal halides, the reactive electrophile is considered to be formed in the interaction of the reagent and the catalyst. First the highly polarized donor–acceptor complex 1 is formed, which can further give other complexes and ion pairs.21 The various possible intermediates are depicted in Scheme 8.1 . Spectroscopic and kinetic data show the presence of these species in the reaction mixture. The scheme includes acyl cation 2, which is usually regarded as the reacting species in aromatic Friedel–Crafts Acylations and forms the σ complex upon interacting with the aromatic compound.6,22,23

  Sign up to read

  Learn more about book
• 

  eBook - PDF

  Chemistry, 5th Edition

  • Allan Blackman, Steven E. Bottle, Siegbert Schmid, Mauro Mocerino, Uta Wille(Authors)
  • 2022(Publication Date)
  • Wiley

    (Publisher)

  Increasing reactivity towards nucleophilic acyl substitution amide ester acid halide anhydride NH 2 R O ORʹ R O X R O O R O R O Figure 23.4 gives a summary of key examples of nucleophilic acyl substitution reactions that the carboxylic acid family can undergo. The amides (Y = NH 2 ), however, follow this general scheme only for the hydrolysis reaction (addition of water). All these will be discussed in more detail later in this chapter. FIGURE 23.4 Key examples of nucleophilic acyl substitution reactions that occur for the carboxylic acid family C R Y O C R OR O esters C R OH O acids C R NH 2 O amides acid derivatives ROH Grignard reagents reduction H 2 O NH 3 C R R′ O ketones C R H O aldehydes reacts further tertiary alcohols primary alcohols reacts further Acid halide formation Among the acid halides, acid chlorides are the most frequently used in the laboratory and in industrial organic chemistry. Recall that alcohols can be converted into chloroalkanes by treatment with thionyl chloride, SOCl 2 , or with phosphorus chlorides, PCl 3 or PCl 5 . These reagents also convert the OH group of a carboxylic acid into a chloride, which is another example of a nucleophilic acyl substitution reaction. The most common way to prepare an acid chloride is to treat a carboxylic acid with thionyl chloride. OH O + SOCl 2 thionyl chloride butanoic acid Cl O + SO 2 + HCl butanoyl chloride CHAPTER 23 Carboxylic acids and their derivatives 1203 WORKED EXAMPLE 23.6 Formation of acid chlorides Complete each of the following equations. (a) OH O + SOCl 2 (b) OH O + PCl 5 Analysis In this type of question, you should try to classify the reagent according to its purpose. In these examples, the reagents convert OH groups to chlorides. Solution (a) Cl O + SO 2 + HCl (b) Cl HCl O + + POCl 3 Is our answer reasonable? The two principal reactions of carboxylic acids are breaking the OH bond (acid dissociation) and breaking the COH bond (nucleophilic acyl substitution).

  Sign up to read

  Learn more about book
• 

  eBook - PDF

  Industrial Arene Chemistry

  Markets, Technologies, Sustainable Processes and Cases Studies of Aromatic Commodities, 4 Volume Set

  • Jacques Mortier(Author)
  • 2023(Publication Date)
  • Wiley-VCH

    (Publisher)

  769 Section 4 4.2. Acylation and Carboxylation 771 27 Acylation of Arenes Chandrakanth R. Gadipelly 1 , Gunjan Deshmukh 2 , Suresh Bhargava 3 , Selvakannan Periasamy 3 , and Lakshmi Kantam Mannepalli 4 1 Technion – Israel Institute of Technology, Department of Chemical Engineering, Sderot David Rose, Haifa, 3200003, Israel 2 Queen’s University, Department of Chemical Engineering, School of Chemistry and Chemical Engineering, 39 Stranmillis Road, David Keir Building, Belfast BT9 5AG, United Kingdom 3 Royal Melbourne Institute of Technology (RMIT University), Centre for Advanced Materials and Industrial Chemistry (CAMIC), School of Applied Sciences, 124 La Trobe St, Melbourne VIC, 3001, Australia 4 Institute of Chemical Technology, Department of Chemical Engineering, Nathalal Parekh Marg, Matunga, Mumbai, 400019, India 27.1 Introduction Charles Friedel and James Mason Crafts discovered in 1877 that anhydrous AlCl 3 could be used as a condensing agent for the synthesis of an infinite number of hydrocarbons [1, 2]. Not only AlCl 3 , they also reported on the use of ferric and zinc chlorides as well as double salt of sodium aluminum chloride, but these were less reactive than AlCl 3 . During their 14 years’ work in this area, they extended the studies to various fields, viz. reactions of organic halides and unsaturated compounds with aromatic and aliphatic hydrocarbons; reactions of acid anhy- drides with aromatic hydrocarbons; reactions of oxygen, sulfur, sulfur dioxide, carbon dioxide, and phosgene with aromatic hydrocarbons; cracking of aliphatic and aromatic hydrocarbons; and polymerization of unsaturated hydrocarbons. Thus even in the early stage of the discovery, the wide scope of the reaction was realized, and during the last 140 years the scope and application of the reaction has proliferated tremendously covering every conceivable variation of reagent, catalyst, and reaction parameters.

  Sign up to read

  Learn more about book
• 

  eBook - PDF

  Solomons' Organic Chemistry

  • T. W. Graham Solomons, Craig B. Fryhle, Scott A. Snyder(Authors)
  • 2017(Publication Date)
  • Wiley

    (Publisher)

  780 CHAPTER 17 CARBOXYLIC ACIDS AND THEIR DERIVATIVES: Nucleophilic Addition–Elimination at the Acyl Carbon If we follow the reverse reactions, we have the mechanism for the acid-catalyzed hydro- lysis of an ester: Acid-Catalyzed Ester Hydrolysis OR′ R O OH R O H 3 O + + + H 2 O R′O—H Whether we synthesize or hydrolyze an ester depends on the conditions we choose. If we want to esterify an acid, we use an excess of the alcohol and, if possible, remove the water as it is formed. If we want to hydrolyze an ester, we use a large excess of water; that is, we reflux the ester with dilute aqueous HCl or dilute aqueous H 2 SO 4 . Steric factors strongly affect the rates of acid-catalyzed hydrolyses of esters. Large groups near the reaction site, whether in the alcohol component or the acid component, slow both reactions markedly. Tertiary alcohols, for example, react so slowly in acid- catalyzed esterifications that they usually undergo elimination instead. However, they can be converted to esters safely through the use of acyl chlorides and anhydrides in the ways that follow. Esters from Acyl Chlorides • The reaction of acyl chlorides with an alcohol or a phenol is one of the best ways to synthesize an ester. The reaction of an acyl chloride with an alcohol or a phenol to form an ester occurs rapidly. Pyridine is often added to the reaction mixture to react with the HCl that forms. (Pyridine may also react with the acyl chloride to form an acylpyridinium ion, an inter- mediate that is even more reactive toward the nucleophile than the acyl chloride.) Cl R R O O + R′ O H O R′ pyridine + Cl − + pyr-H + Specific Example EtOH Benzoyl chloride + + Cl − + pyr-H + Ethyl benzoate (80%) Cl O OEt O pyridine Esters from Carboxylic Acid Anhydrides Carboxylic acid anhydrides also react with alcohols and phenols to form esters in the absence of an acid catalyst.

  Sign up to read

  Learn more about book
• 

  eBook - PDF

  Principles of Peptide Synthesis

  • Miklos Bodanszky(Author)
  • 1984(Publication Date)
  • De Gruyter

    (Publisher)

  To answer this question one has to call the attention to the process of activation, to reactions which convert the carboxyl group to a reactive derivative. For the preparation of acid chlorides, for example, the protected amino acid or peptide is treated with phosphorus pentachloride or thionyl chloride. Such highly reactive materials can affect side chain functions, e.g. they can convert the carboxamide group in asparagine residues to a nitrile: CH2-C0NH2 CH2-CN -NH-CH-CO- - N H - C H - C O - It is obvious, therefore, that not only the coupling reaction itself has to be carried out under mild conditions, but the process of activation as well. In this respect the acid chloride method is rather unattractive. Even if less drastic reagents are used for the preparation of carboxylic acid chlorides, the reactivity of the chlorides themselves is still too high. This renders them sensitive also to nucleophiles which are less reactive than amines, including water. Unless anhydrous conditions are maintained, Acylation of an amine with a carboxylic acid chloride is accompanied by hydrolysis of the latter: R-CO-Cl + H2NR' »• R-CO-NH-R' R-CO-Cl + HOH R-C00H Even more disturbing is the possibility of intramolecular attack on the acid chloride grouping by a weak but favorably placed nucleophile within the (U h SI u , R - C - N - R ' a 1 1 X H R - C - N - R ' + (+HX) H 10

  Sign up to read

  Learn more about book