Trifluoromethanesulfonic Acid as Acylation Catalyst: ...

Many kinds of acid-promoted acylations have been developed in order to improve their reactivity and selectivity, and some of these activators have been applied to industrial processes [ 6 7 ]. A comparative study of the catalytic activities of various acids in acylation has demonstrated that trifluoromethanesulfonic acid (triflic acid, TfOH) is far superior to all other Lewis and Brønsted acids tested [ 8 ]. TfOH is a perfluoroalkanesulfonic acid [ 9 ] that is extremely thermostable and highly resistant to decomposition by aqueous bases [ 10 ]. The synthesis of this acid was first reported in 1954 [ 8 10 ]. Since then, the novel properties of TfOH have been developed for modern chemical applications [ 11 ]; thus, comprehensive discussions of its utilization in various reactions and applications have been published [ 5 13 ]. From the point of view of TfOH as a catalyst for- or-acylation, consideration of comprehensive substrates with the reaction condition are needed to achieve optimum conditions. Recently, the general trends for various substrates- or-acylation catalyzed by TfOH are carried out, not only by the simple arenes with ordinary acyl component utilization, but also with extraordinary substrates to achieve efficient reactions. Therefore, the use of TfOH as a catalyst has broadened. In this review, the catalytic activity of TfOH in- or-acylation is discussed. The recent progress of TfOH as a promising catalyst for both Friedel–Crafts acylation and the Fries rearrangement, where esterification (-acylation) plays an important role to connect these two reactions (from the point of view of phenol and phenol derivatives), is described. Furthermore, the controllable TfOH catalytic system for-acylation and/or-acylation of various substrates is also discussed in this review.

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The widely used-acylation, Friedel–Crafts acylation [ 1 2 ] and Fries rearrangement [ 2 ] of aromatic compounds are efficient methods that result in satisfactory product yields. The fundamental feature of these reactions is the use of a homogeneous or heterogeneous Lewis or Brønsted acid that catalyzes the reaction of the acylating agent with the corresponding substrates. Conventionally, the Friedel–Crafts acylation of aromatic derivatives with acyl chloride or anhydrides requires at least 1 equiv. of AlCl 3 ]. Up to now, an improvement on this reaction is continuing at the time of writing this review. The Fries rearrangement, a typical rearrangement of a phenyl ester to- or-hydroxyphenyl ketone, has been carried out with a number of esters that differ in their phenolic and carboxylic acid substituent [ 4 ]. When phenol and phenol derivatives react with acylating reagents in the presence of appropriate catalyst, they can form aryl ketones via-acylation of the aromatic ring ( Figure 1 a), as well as form phenyl esters via-acylation ( Figure 1 b). In the reaction, phenyl ester derivatives can also undergo Fries rearrangement ( Figure 1 c). Direct phenol-acylation and Fries rearrangement usually compete with one another, and are difficult to distinguish from their reaction mechanisms [ 5 ].

A bifunctional substrate for both the acylation and alkylation of aromatic compounds draws a lot of attention for the proposes of useful cyclic aromatic ketones formation [ 55 ]. The process, known as cyclic acylalkylation, can be formed by the TfOH catalytic system under forced conditions. A high temperature and excess catalyst suppresses the competitive intermolecular reaction to make the cyclization possible. The reaction between aromaticswith unsaturated carboxylic acidscatalyzed by TfOH has been found to produce 1-indanone (= 0) or 1-tetralone (= 1) forms of Scheme 7 ) [ 55 ]. The high temperature (at 80 °C) contributes to the induction of the cyclic acylalkylation in this reaction. In comparison, a low temperature (at 20 °C) favors the multiple terminals acylation of the alkyne moiety and carboxylic moiety of unsaturated carboxylic acid. Moreover, thiochroman-4-ones, which are valuable synthons and important precursors in organic syntheses, are generally synthesized via a multistep reaction; a one-pot approach was uncovered through the use of TfOH [ 56 ]. One-pot cyclic acylalkylation of thiophenolsand crotonic or methacrylic acid (or) under microwave irradiation and in the presence of excess TfOH gives good yields of thiochroman-4-onesand Scheme 8 ).

The use of the (3-trifluoromethyl)phenyldiazirinyl (TPD) group as a photoreactive group in photoaffinity labeling confers selectivity for probe activation without damaging the peptides and proteins under radiation of 350 nm wavelength [ 48 53 ]. The strategy for the synthesis of homophenylalanine or bis-homophenylalanine containing TPD moiety starts with the introduction of a TPD moiety in anisoleinto an aspartic acid analogue 48 ] or a glutamic acid analogue 46 ] ( Scheme 6 b). In this reaction, high temperatures can result in the decomposition of the starting materialdue to the thermolability of TPD under strongly acidic conditions [ 50 54 ]. A temperature of 0 °C is optimal for synthesis using these valuable heat-sensitive aromatic compounds. Furthermore, the reaction betweenanddid not proceed when neat TiClwas used, whereas utilization of TfOH afforded the acylated productup to a 68% yield. The acylated productsare intermediates that can be reduced and deprotected to produce the photoaffinity labeling probes based on homophenylalanine or bis-homophenylalanine derivatives. The mild conditions offered by TfOH catalysis can also be applied to construct not only one, but also two kinds of photophores to introduce in one probe. The strategy for this synthesis is the direct acylation of benzoyl chloride containing TPDand-protected phenylalanineat room temperature ( Scheme 6 c). Enhancement of this reaction was evidenced by no decomposition of the diazirine moiety (product); and no loss of optical purity was observed after the deprotection of productby NaOH (99% ee).

Photoaffinity labeling is a useful biochemical technique for investigating the structural and functional relationships between small biologically active compounds and biomolecules such as proteins (enzymes), RNA, and DNA [ 47 48 ]. In recent years, our laboratory has developed various photophores such as phenylazide, phenyldiazirine, and benzophenone for use in this type of analysis. One of these potential photophores is directly constructed from the benzophenone moiety on phenylalanine using a Friedel–Crafts reaction. Due to the low solubility of phenylalanine derivatives in organic solvents for direct-acylation [ 49 ], neat TfOH was used [ 50 ]. The neat TfOH catalytic system enabled the direct construction of a benzophenone moiety on optically pure phenylalanine via stereocontrolled Friedel–Crafts acylation ( Scheme 6 a). When benzoyl chlorideand phenylalanine derivativeswere used for the reaction system, a complex reaction mixture was observed with a low yield of the desired product. When-protected phenylalaninewas used to suppress any competing reactions, it was found to increase the product yield without any optical loss (up to 40% yield ofwas achieved with 98% ee). Here, benzoic anhydride [ 51 ] can also be used for the production of benzophenone derivatives via direct-acylation. Reaction of this compound with-protected phenethylamine using neat TfOH resulted in a good yield (86%) at room temperature.

In contrast to other catalysts for the Friedel–Crafts acylation, TfOH can behave both as a catalyst and solvent because of its high dissolving capacity [ 12 ]. Aspartic anhydride derivatives(1 equiv.) can dissolve well in TfOH, and the resulting homogenous system allows fast reaction with benzene(1 equiv.), thus forming(major product) orwithin only an hour ( Scheme 5 b). Moreover, both aspartic acid derivative 45 ] and glutamic acid derivative 46 ] are also potential acyl donors for direct-acylation for the synthesis of homophenylalanine or bis-homophenylalanine. Neat TfOH can catalyze acylation of the aromatic derivativesby the acyl donors Scheme 5 c) with a good yield of acylated productand a relatively short reaction time. Furthermore, this reaction is environmentally friendly since it does not use excess reagent. In the homogeneous reaction system, acyl donorscan undergo acylation smoothly without any hydrolysis and retain its enantiomer skeleton even after the reaction. TfOH acts as a catalyst and solvent, thus enhancing the effectiveness and efficiency of synthesis of the aryl keto α-amino acids by direct-acylation.

Homophenylalanine or bis-homophenylalanine, which differ in the addition of methylene or ethylene in the side chain of phenylalanine, is a functional biomolecule and the asymmetric synthesis of both compounds is important. One of the potential skeletons used in the synthesis of aryl keto α-amino acids is formed by using aspartic anhydride, which can undergo direct-acylation to arenesunder Friedel–Crafts conditions. When AlClwas used as the catalyst for the acylation of aspartic anhydrides with arenes, common organic solvents such as CHCl 41 ] or MeNO 42 ] were used under reflux for extended periods. When organic solvent was eliminated, arenes in excess amount were used because of their low solubility to solve some aspartic acid derivatives. For example, >50 equiv. of arenesis needed to react with aspartic anhydride Scheme 5 a) in order to produce aryl ketoneor(wherein the ratio depends on the type of aspartic anhydride derivative used in the reaction) [ 43 44 ]. Maintaining the ratio of aspartic anhydridetoat a 1:1 ratio, as well as using AlClin CHClfor 12 h have also been shown to cause no reaction and the acyl donor remained precipitated. This result implies that the full dissolution of this system is essential and an excess amount of arenes is required for the reaction. Similarly, no reaction was observed when the conventional catalyst AlClwas replaced with TiCl, sulfuric acid, or trifluoromethanesulfonic anhydride (TfO) [ 45 ].

Metal triflates can promote the acylation of benzene, chlorobenzene or fluorobenzene using benzoyl chloride [ 38 ] and alcohol using benzoic anhydride [ 39 ]. This reaction is known to be catalyzed mainly by TfOH (either added or released at the onset of the reactions); therefore, a metal-free reaction system utilizing neat TfOH is still of interest. The synthesis of aryl keto α-amino acids through straightforward and convenient methods has attracted more attention [ 12 ] because these compounds are convenient intermediates that can be directly converted into the desired α-amino acids.-acylation involving the aromatic compounds and side chains of carboxylic derivatives is a potential pathway for the synthesis of aryl keto α-amino acids that obviates the requirement of special reagents or precursors. This reaction may also be used for the asymmetric synthesis of α-amino acids. Therefore, due to these purposes, aspartic acid derivatives have become popular acyl donors and have been well studied.

The development of an efficient intramolecular Friedel–Crafts reaction of 1-(2-isocyanatoethyl)benzene derivativesusing TfOH as catalyst ( Scheme 4 ) [ 37 ] demonstrates the vast applications of the catalytic system based on neat TfOH. In contrast to neat TfOH utilization, other catalysts such as AlCl, ZnCl, TiCl, or sulfuric acid require the use of an organic solvent for this intramolecular reaction. The high temperatures and reflux conditions needed for these catalysts still result in the low yield of the desired productand require a long reaction time. In fact, under certain conditions, the AlCland ZnClcatalytic systems do not lead to the desired product

The TfOH catalytic system has been of interest because of its two properties that can enhance the reaction’s efficiency: (1) a solvent-free reaction that can be an alternative environment-friendly organic synthetic pathway; (2) a mild conditions, which are advantageous to reactions of valuable heat-sensitive substrates. For many years, the biotin–(strept)avidin system has been widely used for various applications. Biotin is a complex derivative of valeric acid that possesses a high binding affinity to avidin (a protein found in egg white) and streptavidin (a protein found in Streptomyces avidinni) [ 35 ]. Previously, mixed anhydride generated in situ from biotin using the TfOH/TFAA catalytic system was reported to react with electron-rich acyl acceptors (ferrocene, ruthenocene, and pyrene) [ 33 ]. The selected arenes are very reactive in the Friedel–Crafts acylation, thus providing an opportunity for using biotin in these reactions. At present, our laboratory can use neat TfOH for acylation reaction using acid chloride of biotinas an acyl donor. It is estimated that the high reactivity to acylation, which is the key role in this reaction, is not only due to the reactive skeleton of the acyl acceptor, but also the proper selection of the acyl donor. As a result, the acid chloride of biotinreadily reacts with the less-electron-rich acyl acceptor, forming acylated productin the presence of neat TfOH ( Scheme 3 ) [ 36 ]. From the point of view of fundamental biological activity with the replacement of an avidin specific bound compound, it suggests that aromatic derivatives of acylated biotin have enough biological activity against the biotin skeleton. Furthermore, the resulting aromatic derivatives of acylated biotin can possibly be explored for functional bioanalysis-tag in the future.

The application of functionalized or biologically important acids or their derivatives from the Friedel–Crafts reaction has been carried out by utilizing the so-called active esters. These esters (and) are readily accessible, stable, and exhibit high electrophilic reactivity toward amino groups. The TfOH system has also been used to catalyze the direct acylation of the electron-rich aromatic rings ferroceneand pyreneusing tetrafluorophenyl estersand-hydroxysuccinimidyl esters 31 ]. Compoundswere found to be less reactive than the-hydroxysuccinimidyl esters Table 2 , entries 9–12). Despite the use of an excess of these esters, the acylation process was observed to be selective without formation of the diacylated compounds. Nevertheless, acylation using these esters as electron-rich donors seems to be identical with the process induced using TfOH as the catalyst. Another study found that acylation of an electron-rich acceptor using a carboxylic acid requires the combination TfOH and trifluoroacetic anhydride (TFAA) [ 32 ]. This study also claimed that efficient acylation had been achieved due to the high reactivity of the electron-rich acceptors (e.g., ferroceneand pyrene, which are, respectively, 3.3 × 10and 220 times more reactive than benzene) [ 33 ]. When a stochiometric amount of TFAA is reacted with carboxylic acid, the reaction mixture will form acyl trifluoroacetate intermediates. Next, these reactive electrophiles will react with the aromatic compound through a process that usually requires a strong acid (TFA formed in the reaction between carboxylic acid and TFAA may be not sufficiently strong to complete the reaction [ 32 ]). Therefore, TfOH is needed in order to accelerate the acylation. Furthermore, the TfOH/TFAA catalytic system can also be applied to a vast number of acylation, such as the acylation of metallocenes with alkynoic acids which results in an acylated product that can undergo the impressive azide-alkyne “click” chemistry [ 34 ].

In 1986, Roberts and Wells first used the TfOH catalytic system in the acylation of electron-rich metallocene and pyrenes using acetic anhydrideas an acyl donor ( Table 2 , entries 1 and 2) [ 27 ]. Treatment of excess acetic anhydride(~6 equiv.) with 1 equiv. of TfOH at room temperature improved the acylation of ferrocenesandin comparison with the reaction using approximately 1 equiv. of the conventional catalyst AlClat room temperature [ 28 ] or at ~50 °C [ 29 ]. This system has been extended for the use of a limited number of possible acylation positions for metallocenesand 30 ]. Monosubstitution of an acyl group at the two-position ( Table 2 , entries 3 and 4) occurs with the TfOH catalytic system, in contrast to the disubstitution achieved with AlCl. Phenyl estersandhave also been used as acylating agents for metallocene (, and) and pyrene () ( Table 2 , entries 5–8). The substituted aromatic derivative of phenyl-methoxybenzoic acid (), which is more electron-rich than its corresponding phenyl benzoate (), had higher reactivity in the acylation of both ferroceneand pyrene Table 2 , entries 5 and 8).

In Table 1 , the syntheses of 3-spirocycliquinon-4-ones involving intramolecular rearrangement of 3-spirocyclic β-lactam, which are used in the syntheses of important heterocyclic scaffolds, are described. Conditions for this synthesis uses quinolonesandwhich have been optimized by using a combination of 20 mol % TfOH and 30 mol % FeCl Table 1 , entries 3 and 4) [ 26 ]. Utilization of FeClwithout a Brønsted acid led to only 9% yield from quinolonesand, along with unreacted starting material. Due to the lower requisite amount of Brønsted acid and the lower reaction temperature required to effect high selectivity, TfOH is preferable to other acids such as TFA for these reactions.

TfOH-catalyzed aromatic acylation using β-lactams as the acyl donors has broadened the application of TfOH as a catalyst for intramolecular-acylation. The typical Fries rearrangement of-arylazetidinonescan be carried out using TfOH to produce quinolonesat excellent yields ( Table 1 , entry 1). Most protocols for quinoline-4-one synthesis require multistep procedures, a large amount of catalyst, and have low yields [ 23 24 ]; to address these limitations, TfOH has been utilized [ 25 ]. The rearrangement of-3-butadienyl-2-azetidinonesresulted in quinoline-4-onesin moderate yields (55%–65%; Table 1 , entry 2). Initial protonation of the starting materialcan lead to the generation of the carbenium ion intermediate, which can undergo the Fries rearrangement and subsequent oxidation to quinoline-4-ones. However, using TfOH can simplify the rearrangement process under mild conditions to a one-step procedure.

A recent study has reported the use of TfOH for the-acylation of arenes with twisted amides Figure 4 a) [ 22 ]. The acylation of benzenewith two different types of amide, i.e., benzoyl 2,5-pyrrolidinedioneand benzoyl 2,6-piperidinedione, had afforded ketone productin good to excellent yields. Different to previous amides-type of acyl donor, β-lactams Scheme 2 ), that involved the highly reactive acyl carbonium ion intermediate [ 21 ], the acylation of arenes with twisted amidesoccurred exclusively at the endothermic N–CO bond. The high reactivity of the twisted amide bond might be tuned by N–C(O) bond rotation, and selective-protonation of the amide bond under acidic conditions may enhance the potential for nucleophilic addition ( Figure 4 b). Therefore, the selection of the acid to promote this reaction is important. For example, acid-catalyzed acylation of benzenewith benzoyl 2,6-piperidinedioneis more efficient using TfOH, which results in up to 90% yield of ketone product Figure 4 c), than the other tested catalysts, such as HBF, HCl, TFA, BF·EtO, and TiCl. Moreover, the TfOH catalytic system is also suitable for the acylation of benzene with twisted amides, in which the aromatic rings carry various substituents ( Figure 4 a). The mild condition using TfOH as catalyst is compatible with the wide array of functional groups introduced in twisted amidesindicated by up to a 70% yield of ketone product

Efficient catalysis of reactions involving esters as acyl donors by using TfOH have led to the use of TfOH for the synthesis of β-amino aryl ketone derivatives from the acyl donors β-lactams () [ 20 21 ]. The TfOH-catalyzed reaction between β-lactamsand arenesproduces the desired β-amino aryl ketone derivativesin moderate to high yields ( Scheme 2 ). Meanwhile, no reaction was observed at room temperature using other common catalysts for the Friedel–Crafts acylation, such as AlCl, methanesulfonic acid (MSA), trifluoroacetic acid (TFA), BF·OEt, or SnCl. Reflux conditions did not produce the desired β-amino aryl ketone compounds; therefore, utilization of TfOH for this reaction at room temperature is preferred.

A typical definition of the intermolecular-acylation is the addition of acyl groups to aromatic derivatives, which is conducted by an activator. Conventional acylation includes the use of simple arenes (both electron-rich and electron-poor) such as benzene, toluene, and xylene, which act as acyl acceptors, as well as typical acyl donors such as acyl chloride, carboxylic anhydride, esters, and carboxylic acid. The TfOH catalytic system has made the exploration of different acyl donors more feasible for-acylation, thus increasing the number of potential donors for this reaction. Direct-acylation of aromatic compounds using benzoic acid esters is extending this exploration series. At 85 °C, excess TfOH (5 equiv.) has been used for direct-acylation of methyl benzoate(2 equiv.) and aromatic derivatives, thus forming the benzophenone derivatives 19 ]. In this reaction, no further electrophilic reaction of benzophenones with the aromatics was observed ( Scheme 1 a). Even highly deactivated nitrobenzeneand benzotrifluorideacted as acyl acceptors, affording the corresponding three-substituted benzophenonesandin high yield. Furthermore, the TfOH system can also catalyze the acylation of benzenewith diesters such as 1,4-dimethyl terephthalate, which results in a mixture containing the major products 4-benzoyl methyl benzoateand 1,4-dibenzoyl benzene, under similar reaction conditions (i.e., reaction for 8 h) ( Scheme 1 b).

A study in 1972 using a low proportion of TfOH (~1 wt %) for the acylation of-xylenewith benzoyl chloride 3 ] found that this acid produced a higher yield of productin comparison with other tested catalysts, including the conventional catalyst AlCl Figure 3 ). Since then, the catalytic activity of TfOH has been extensively studied. In recent decades, research into TfOH not only focused on determining its optimal proportion for high efficiency acylations, but also in broadening the utilization of vast substrates, which contribute to new synthetic pathways, and the comprehensive study of suitable reaction conditions to optimize its application exploitation. For example, sterically hindered aromatic ketones and carboxylic acids can undergo either protodeacylation or decarboxylation, which are typically accompanied by side reactions in the presence of TfOH (at 110 °C) [ 17 ]. As the direct mechanism of-acylation is identical to that of other reactions, there is a need to examine the selection of aromatic compounds used in these reactions [ 18 ]. A summary of the general characteristics of the TfOH catalytic system for-acylation in this review is expected to discover excellent findings for TfOH catalytic activity in the future.

Carbon–carbon bond formation in Friedel–Crafts acylation ( Figure 1 a) is one of the most important routes for preparing various ketones; especially in the synthesis of aryl ketones. In the case of the acylation of phenol, it has been extensively studied for- or-hydroxyphenyl ketones synthesis and since it employs more readily available and less expensive raw materials, direct Friedel–Crafts-acylation might offer a convenient approach. Generally, the Friedel–Crafts acylation is carried out using acylating reagents such as acyl chlorides, carboxylic anhydrides or carboxylic acids in the presence of a Lewis or Brønsted acid. TfOH possesses a large negativevalue (−14.1) [ 9 14 ], which is stronger than other Lewis acids. Therefore, it is categorized as a superacid and expected to be an effective catalyst for Friedel–Crafts-acylation. A comparative study using sulfuric acid, TfOH, and three other perfluorinated sulfonic acids synthesized by Harmer et al. [ 15 ] in the acylation of anisole Figure 2 a) proved this expectation. Moreover, the Fries rearrangement of phenyl acetate Figure 2 b) also shows high efficiency of TfOH utilization as a catalyst as it is 100 times stronger than sulfuric acid [ 13 16 ] and is a commercially available reagent which can be readily used for these reactions.

TfOH as an efficient catalyst in the esterification reaction was also studied by Shibata et al. [ 60 ]. Reactions between various benzoic acid derivatives () and octan-1-ol () were carried out using a catalytic amount of TfOH in 1,1,1,3,3-pentafluorobutane as a solvent. The unique properties of TfOH make it a more active catalyst than sulfonic acid; thus, 0.2 mol % of TfOH is sufficient for the excellent conversion of the reactants to Scheme 10 a). This condition is also suitable for the-acylation of either the diacidwith an alcohol Scheme 10 b), or the diolwith carboxylic acid Scheme 10 c). Both of these reactants were converted to their diesters,or, respectively, with excellent yields without the need for extended reaction times.

Rotaxanes are molecules composed of a linear dumbbell-shaped substituent flanked by one or more macrocycles. For many years, chemists have been intrigued by the challenge of synthesizing these mechanically interlocked molecules; traditional synthetic methods can only produce poor yields of rotaxanes [ 58 ]. The selective-acylation of diethanolamineby aromatic acid anhydridewas carried out in the presence of 1.5 equiv. of TfOH and dibenzo-24-crown-8 to afford [2]rotaxaneat 0 °C ( Scheme 9 ). The use of TFA and MSA did not allow the formation ofand only formed the esterification product from starting material. Relative to the acidity of other catalysts, TfOH is sufficient for the protection of the amino group via protonation and esterification. Thus, the TfOH catalytic system enables high production yields ofat low temperature [ 59 ].

Esterification, ester condensation, or so-called-acylation feature is clearly identified as the general utilization of carboxylic acids and alcohols that are usually activated by Brønsted acids. Thus, esterifications do not require superacid catalysis [ 9 ]. Indeed, typical superacids have been studied and observed as convenient catalyst which can improve the method for direct esterification, without any changes of catalytic activity even for prolonged reaction times [ 9 57 ]. This characteristic has thus led to an interest in the use of TfOH as a catalyst for-acylation.

4. Special Features of TfOH in Selective

C

- and/or

O

-Acylations

C

- and/or

O

-acylations using various substrates naturally depend on the acyl donor and acceptor used. Both reactions can be controlled by changing the reaction temperature, which is inherently related to the reaction time. The catalyst, and sometimes the solvent, also plays an important role in these reactions. One of the unique characteristics of TfOH as a catalyst is that conditions for TfOH-catalyzed acylation may be determined and adjusted to increase the reaction’s selectivity. Denoting into this term, it can be mentioned as a “special” catalytic feature of TfOH. For example, TfOH can be used in the transacylation and deacylation between several types of hindered acetophenones and anisole 1 at 70 °C in the presence of imidazolium-based ionic liquids [

- and/or-acylations using various substrates naturally depend on the acyl donor and acceptor used. Both reactions can be controlled by changing the reaction temperature, which is inherently related to the reaction time. The catalyst, and sometimes the solvent, also plays an important role in these reactions. One of the unique characteristics of TfOH as a catalyst is that conditions for TfOH-catalyzed acylation may be determined and adjusted to increase the reaction’s selectivity. Denoting into this term, it can be mentioned as a “special” catalytic feature of TfOH. For example, TfOH can be used in the transacylation and deacylation between several types of hindered acetophenones and anisoleat 70 °C in the presence of imidazolium-based ionic liquids [ 61 ]. The high yield conversion (>98% for one moiety of acyl group in hindered acetophenones), high selectivity, minimal side reactions, and the obviated use of excess TfOH illustrate its superiority over other acids utilized in these reactions.

94, which contains two phenyl ring moieties (which are denoted as rings A and B, 94 into ring A to form arylcoumaranone 95 or ring B to form dibenzoxepine 96 can be controlled (94 can form and then further transformed into an ionic intermediate by removing the possible leaving group as –OTf. This ionic intermediate exhibits the less steric hindrance; therefore, the formation of 95 or 96 is achievable, depending upon the conditions. A low temperature is preferred for the selective formation of 95 (96 (

The selective intramolecular cyclic acylation of the 2-arylphenoxyacetic acid, which contains two phenyl ring moieties (which are denoted as rings A and B, Figure 5 ) [ 62 ], is another unique characteristic of the TfOH catalytic system. Cyclic acylation of the carboxylic moiety ofinto ring A to form arylcoumaranoneor ring B to form dibenzoxepinecan be controlled ( Figure 5 ). Under the action of the strong acid TfOH, the intermediate of mixed anhydride withcan form and then further transformed into an ionic intermediate by removing the possible leaving group as –OTf. This ionic intermediate exhibits the less steric hindrance; therefore, the formation oforis achievable, depending upon the conditions. A low temperature is preferred for the selective formation of Figure 5 a) using a similar amount of TfOH (30 equiv.) added dropwise. Meanwhile, under the same temperature, utilization of a low amount of TfOH (10 equiv.) can result in the formation of Figure 5 b).

O

- and

C

-arylglycoside is hampered by the low solubility of the unprotected aromatic glycosides in the reaction medium and the competitive deglycosidation under acidic conditions for

O

-glycosides. TfOH was found to easily dissolve the carbohydrates without causing their decomposition. The low solubility of unprotected aromatic glycosides can be overcome by using TfOH as a Friedel–Crafts acylation promoter. This technique can be extended to other reactions such as direct acylation of

O

- and

C

-arylglycosides. The Friedel–Crafts acylation of the aromatic moiety and

O

-acylation of the glucose moiety of aryl glycoside is dependent upon the proportion of TfOH used [

d

-glucoside 97 with acetyl chloride 98 in the presence of excess TfOH (16 equiv.) can result in the production of 98 with good yield (

O

-acylation of the glucose moiety. Treatment of 97 with 1.6 equiv. of TfOH, produces only the per-

O

-acetylated compound 100, indicating that the

O

-acylation is faster than the Friedel–Crafts acylation. This result is supported by the re-treatment of 100 with a large amount of TfOH, which afforded an ~90% yield of the Friedel–Crafts product 99.

The derivatization of- and-arylglycoside is hampered by the low solubility of the unprotected aromatic glycosides in the reaction medium and the competitive deglycosidation under acidic conditions for-glycosides. TfOH was found to easily dissolve the carbohydrates without causing their decomposition. The low solubility of unprotected aromatic glycosides can be overcome by using TfOH as a Friedel–Crafts acylation promoter. This technique can be extended to other reactions such as direct acylation of- and-arylglycosides. The Friedel–Crafts acylation of the aromatic moiety and-acylation of the glucose moiety of aryl glycoside is dependent upon the proportion of TfOH used [ 63 ]. The reaction of phenyl-β--glucosidewith acetyl chloridein the presence of excess TfOH (16 equiv.) can result in the production ofwith good yield ( Scheme 11 ). In this case, the excess TfOH promotes not only the Friedel–Crafts acylation of the aromatic moiety, but also the-acylation of the glucose moiety. Treatment ofwith 1.6 equiv. of TfOH, produces only the per--acetylated compound, indicating that the-acylation is faster than the Friedel–Crafts acylation. This result is supported by the re-treatment ofwith a large amount of TfOH, which afforded an ~90% yield of the Friedel–Crafts product

C

-acylation of phenol derivatives and acetyl agents and the Fries rearrangement of phenyl ester derivatives via an appropriate catalyst are useful approaches to the synthesis of

o

- or

p

-hydroxyaryl ketones [101 was reacted with 1 equiv. of acetyl chloride 98 using an excess of neat TfOH (>30 mmol),

p

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-hydroxyphenyl ketone 102 was formed (2 to produce

p

-hydroxyphenyl ketone 102 (2 occurs at room temperature under the mild conditions offered by TfOH. The appropriate conditions for catalysis using neat TfOH can also be applied to direct

C

-acylation of acyl chlorides having various side chains to phenol derivatives. Their application to the Fries rearrangement of various phenyl carboxylate derivatives also results in high yield.

The Friedel–Crafts-acylation of phenol derivatives and acetyl agents and the Fries rearrangement of phenyl ester derivatives via an appropriate catalyst are useful approaches to the synthesis of- or-hydroxyaryl ketones [ 1 2 ]. In these reactions, TfOH may act as both catalyst and solvent, resulting in high efficiencies of these reactions. When phenolwas reacted with 1 equiv. of acetyl chlorideusing an excess of neat TfOH (>30 mmol),-hydroxyphenyl ketonewas formed ( Scheme 12 a) [ 64 ]. Despite the reaction being conducted at room temperature, the reaction was relatively fast and had excellent yield. Under the same conditions, neat TfOH can also be used in the Fries rearrangement of phenyl acetateto produce-hydroxyphenyl ketone Scheme 12 b). In contrast to the conventional Fries rearrangement, which usually involves heating the reaction mixture to 80–180 °C [ 2 ], the Fries rearrangement of phenyl acetateoccurs at room temperature under the mild conditions offered by TfOH. The appropriate conditions for catalysis using neat TfOH can also be applied to direct-acylation of acyl chlorides having various side chains to phenol derivatives. Their application to the Fries rearrangement of various phenyl carboxylate derivatives also results in high yield.

m

-cresol 103 using either acetyl chloride 98 (104 (105a/105b ratio of 1.4–2:1) [98 or acetic acid 104 have the same active species that plays an important role in exceeding the reaction. When

m

-tolyl acetate 106 was reacted with TfOH (106 was reported to be faster than the reaction of

m

-cresol 103 and acetic acid 98 in an hour, after 16 h reaction at room temperature the yield of the products was almost the same. These results indicate competition between the Fries rearrangement and hydrolysis of

m

-tolyl acetate 106. However, the hydrolyzed acyl donor again underwent a Friedel–Crafts type reaction with

m

-cresol 103 over an extended period [

The mixed carboxylic trifluoromethanesulfonic anhydride is formed from the reaction of TfOH with acyl chloride [ 65 ] or carboxylic acid [ 66 67 ]. It is known as an extremely powerful acylating agent [ 65 67 ]; its reaction with toluene is highly selective when a bulky side chain is used [ 67 ]. The TfOH catalytic system for acylation of-cresolusing either acetyl chloride Scheme 13 a) or acetic acid Scheme 13 b) has been found to have similar yields of the isomeric products (ratio of 1.4–2:1) [ 64 ]. This result indicates that the acylation of phenolic compounds with either acetyl chlorideor acetic acidhave the same active species that plays an important role in exceeding the reaction. When-tolyl acetatewas reacted with TfOH ( Scheme 13 c), both the Fries rearrangement and hydrolysis were observed. Even though the Fries rearrangement ofwas reported to be faster than the reaction of-cresoland acetic acid 98 in an hour, after 16 h reaction at room temperature the yield of the products was almost the same. These results indicate competition between the Fries rearrangement and hydrolysis of-tolyl acetate. However, the hydrolyzed acyl donor again underwent a Friedel–Crafts type reaction with-cresolover an extended period [ 64 ].

C

-acylation was achieved and the

O

-acylation for the formation of phenyl ester derivatives was also observed (

.

A catalytic amount of TfOH in CH3CN (1%) used in the room-temperature reaction between phenol 101 and acetyl chloride 98 afforded phenyl acetate 2 in excellent yields (98 (3 equiv.) resulted in a quantitative yield of phenyl acetate 2. A high proportion of the acylating agent was utilized to prevent other reactions when the available TfOH in the reaction system was very low. The interaction between CH3CN, which also functions as a solvent, and TfOH has already been studied and a wide variety of complicated structures that can be formed according to the ratio of the two compounds are known [

C

-acylation of phenol 101 with acetyl chloride 98. This study showed that the unique properties of TfOH, which depends on its proportion, affects the phenol 101 acylation process and can be controlled for

C

- or

O

-acylated product synthesis [

O

-acylated product of phenyl acetate 2 is also can be followed by the Fries rearrangement to

p

-hydroxyaryl ketones, which are known as useful reactants and/or intermediates for the manufacture of agrochemicals and pharmaceuticals.

When phenol derivatives were reacted with a selected acyl donor using a catalyst, direct-acylation was achieved and the-acylation for the formation of phenyl ester derivatives was also observed ( Scheme 12 A catalytic amount of TfOH in CHCN (1%) used in the room-temperature reaction between phenoland acetyl chlorideafforded phenyl acetatein excellent yields ( Scheme 12 c) [ 64 ]. Increasing the proportion of acetyl chloride(3 equiv.) resulted in a quantitative yield of phenyl acetate. A high proportion of the acylating agent was utilized to prevent other reactions when the available TfOH in the reaction system was very low. The interaction between CHCN, which also functions as a solvent, and TfOH has already been studied and a wide variety of complicated structures that can be formed according to the ratio of the two compounds are known [ 68 ]. A previous study suggested that an excess amount of neat TfOH, acting as both catalyst and solvent, can catalyze the direct-acylation of phenolwith acetyl chloride. This study showed that the unique properties of TfOH, which depends on its proportion, affects the phenolacylation process and can be controlled for- or-acylated product synthesis [ 64 ]. However,-acylated product of phenyl acetateis also can be followed by the Fries rearrangement to-hydroxyaryl ketones, which are known as useful reactants and/or intermediates for the manufacture of agrochemicals and pharmaceuticals.

C

-acylation of naphthol 107 with acetyl chloride 98 and acetic acid 104, as well as the Fries rearrangement of naphtyl acetate 108 can be conducted by using the TfOH catalytic system (107 required the use of 20% TfOH in a toluene–nitromethane (6.7:1) solution and a temperature of 100 °C (3CN at room temperature produces product 108 (101 acylation with acetic acid 104 by Sobrinho et al. [2 is favored over hydroxyphenyl ketone derivatives at high temperature (>800 K). The product distribution was also very clear in which ~100% formation of hydroxyphenyl ketone derivatives were selective when the temperature was up to 800 K. Therefore, when the utilization of a limited proportion of TfOH was applied to naphthol 107 at a high temperature, the two parallel pathways that resulted in the production of hydroxyaryl ketones [

C

-acylation of phenolic compound. Second is the

O

-acylation of phenolic compounds, which form the ester as an intermediate, and directly transform to hydroxyaryl ketones via the Fries rearrangement. Neat TfOH can also smoothly catalyze the direct

C

-acylation of naphthol 107 and the Fries rearrangement of 108, which affords good yields of the two isomers 109 and 110 (

C

- and/or

O

-acylations can be exploited to obtain the desired aromatic products from thermolabile substrates, an approach that would be of interest for further study.

Direct-acylation of naphtholwith acetyl chlorideand acetic acid, as well as the Fries rearrangement of naphtyl acetatecan be conducted by using the TfOH catalytic system ( Table 3 ). Kobayashi et al. [ 69 ] reported that the direct acylation of naphtholrequired the use of 20% TfOH in a toluene–nitromethane (6.7:1) solution and a temperature of 100 °C ( Table 3 , entry 1). As mentioned above, catalysis by 1% TfOH in CHCN at room temperature produces product Table 3 , entry 2). In a study of thermodynamic analysis of phenolacylation with acetic acidby Sobrinho et al. [ 70 ], they found that temperature played an important role in determining the acylation product; phenyl acetateis favored over hydroxyphenyl ketone derivatives at high temperature (>800 K). The product distribution was also very clear in which ~100% formation of hydroxyphenyl ketone derivatives were selective when the temperature was up to 800 K. Therefore, when the utilization of a limited proportion of TfOH was applied to naphtholat a high temperature, the two parallel pathways that resulted in the production of hydroxyaryl ketones [ 71 72 ] might be pursued (the solvent effect, however, is not discussed here). First is the direct-acylation of phenolic compound. Second is the-acylation of phenolic compounds, which form the ester as an intermediate, and directly transform to hydroxyaryl ketones via the Fries rearrangement. Neat TfOH can also smoothly catalyze the direct-acylation of naphtholand the Fries rearrangement of, which affords good yields of the two isomersand Table 3 , entries 3 and 4). In summary, the controllability of TfOH catalysis in direct- and/or-acylations can be exploited to obtain the desired aromatic products from thermolabile substrates, an approach that would be of interest for further study.

C

- and/or

O

-acylations of phenol 101 are showed in 64,66 (66 is reacted with phenol 101 under neat TfOH at room temperature, the

C

-acylation product, benzyl carbonyl derivative 111, is observed in good yield. The Fries rearrangement step can also be conducted from the phenyl ester 112 by the use of neat TfOH to produce two

C

-acylated isomers 111 (

o

- or

p

-position with ratio of 1.4:1 for compound 111a and 9:1 for compound 111b).

O

-acylation can be proceeded in the reaction between 3 equiv. of acylating agent 66 and phenol 101 by using diluted TfOH in CH3CN (3%–5%) at room temperature, producing the phenyl ester 112 in good yield. The

O

-acylation product can also undergo the Fries arrangement to the regioisomers 111, with isolation yields and proportions identical to those of the direct Friedel–Crafts

C

-acylation products. Compound 111 can then undergo reduction and deprotonation to optically pure multifunctional products, homophenylalanine or bis-homophenylalanine derivatives (>99% ee), which can be used for further analytical studies. Hence, the TfOH catalytic system has a number of functions, acting not only as a catalyst but also as a solvent. Furthermore, it can be controlled for the desired

C

- and/or

O

-acylations products synthesis.

The applications of controlled TfOH-catalyzed- and/or-acylations of phenolare showed in Scheme 14 73 ]. In a previous section, the use of neat TfOH under mild conditions in the acylation of aromatic derivatives using acylating agent Scheme 5 c) is discussed. When 1 equiv. of acylating agentis reacted with phenolunder neat TfOH at room temperature, the-acylation product, benzyl carbonyl derivative, is observed in good yield. The Fries rearrangement step can also be conducted from the phenyl esterby the use of neat TfOH to produce two-acylated isomers- or-position with ratio of 1.4:1 for compoundand 9:1 for compound).-acylation can be proceeded in the reaction between 3 equiv. of acylating agentand phenolby using diluted TfOH in CHCN (3%–5%) at room temperature, producing the phenyl esterin good yield. The-acylation product can also undergo the Fries arrangement to the regioisomers, with isolation yields and proportions identical to those of the direct Friedel–Crafts-acylation products. Compoundcan then undergo reduction and deprotonation to optically pure multifunctional products, homophenylalanine or bis-homophenylalanine derivatives (>99% ee), which can be used for further analytical studies. Hence, the TfOH catalytic system has a number of functions, acting not only as a catalyst but also as a solvent. Furthermore, it can be controlled for the desired- and/or-acylations products synthesis.

Original Russian Text © A.N. Kazakova, A.V. Vasilyev, 2017, published in Zhurnal Organicheskoi Khimii, 2017, Vol. 53, No. 4, pp. 479–502.

Anna Nikolaevna Kazakova was born in 1985 in Sterlitamak. In 2008 she graduated from the Sterlitamak State Pedagogical Academy and in 2011 finished post-graduate courses at the Ufa State Petroleum Technological University. Candidate of chemical sciences. Since 2013 she works as assistant at the Institute of Chemistry, St. Petersburg State University.

Fields of scientific interest: chemistry of halogen-substituted carbocations, synthesis and electrophilic reactions of organofluorine compounds.

Aleksandr Viktorovich Vasilyev was born in 1970 in Leningrad. In 1992 he graduated from the Faculty of Chemistry, St. Petersburg State University. Doctor of chemical sciences, director of the Institute of Chemical Processing of Wood Biomass and Technosphere Safety at the St. Petersburg State Forest Technical University, Head of the Chemistry Department of the St. Petersburg State Forest Technical University, Professor at the Organic Chemistry Department of the St. Petersburg State University.

Fields of scientific interest: electrophilic activation of organic compounds, chemistry of unsaturated compounds, new methods of carbon–carbon bond formation, chemistry of organofluorine compounds, organic synthesis based on natural compounds.

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