Benzoyl chloride, acylation with

A kinetic smdy of the acylation of ethylenediamine with benzoyl chloride (110) in water-dioxane mixtures at pH 5-7 showed that the reaction involves mainly benzoylation of the monoprotonated form of ethylenediamine. Stopped-flow FT-IR spectroscopy has been used to study the amine-catalysed reactions of benzoyl chloride (110) with either butanol or phenol in dichloromethane at 0 °C. A large isotope effect was observed for butanol versus butanol-O-d, which is consistent with a general-base-catalysed mechanism. An overall reaction order of three and a negligible isotope effect for phenol versus phenol- /6 were observed and are consistent with either a base- or nucleophilic-catalysed mechanism. Mechanistic studies of the aminolysis of substituted phenylacetyl chlorides (111) in acetonitrile at —15 °C have revealed that reactions with anilines point to an associative iSN2 pathway. ... 

Investigations into the mechanism of hydrolysis and alcoholysis of acyl halides have been largely concerned with acyl chlorides and in particular with benzoyl chloride and the related aromatic acid chlorides. This was a result of the relatively slow rate of hydrolysis of benzoyl chloride compared with acetyl chloride (although their alcoholysis rates are easily measurable) and it is only comparatively recently90 that stop-flow techniques have been used to measure the faster rate of hydrolysis. However, in spite of this limitation, considerable progress has been made towards elucidation of the mechanism or mechanisms of hydrolysis and alcoholysis of these halides. 

Acyl chlorides and acid anhydrides react with primary and secondary amines without the presence of heat to form amides. Tertiary amines cannot be acylated due to the absence of a replaceable hydrogen atom. With the much less active benzoyl chloride, acylation can still be performed by the use of excess aqueous base to facilitate the reaction. 

The hydrogen atom in the NH group can also be substituted by the acyl residue.229,267-272 Reaction of benzoyl chloride with 5,5-diethyl- and 5-ethyl-5-phenylbarbituric acids proceeds in two steps. In the first step, benzoyl chloride reacts with N-nonsubstituted barbiturates, yielding N-monosub-stituted derivatives (99 R1 = Et, R2 = Et, Ph R3 = PhCO), which then undergo the self-acylation reaction [Eq. (7)]. 

Esterification reactions readily occur in ionic liquids. A simple example is the reaction of acetic, decanoic and octadecanoic acid with alcohols such as methanol, 1-butanol or 1-octanol. Here, Tang et al. used the ionic liquid [H-MIM][BF4] (this is a simple mixture of 1-methylimidazole and tetrafluoroboric acid) as a solvent and catalyst for the reaction [189]. Singer and coworkers have shown that benzoyl chloride reacts with ethers to give alkyl benzoates [190] in chloroaluminate(iii) ionic liquids. This reaction results in the acylative cleavage of ethers, and a number of reactions with cyclic and acyclic ethers were investigated in the ionic liquid [EMIMjl-AICI3 (X = 0.67). Two examples are shown in Scheme 5.2-79. 

Reductions. In contrast to hydrosilylation reactions catalyzed by metal chlorides, aldehydes and ketones are rapidly reduced at rt by Triethylsilane and BF3-OEt2, primarily to symmetrical ethers and borate esters, respectively. Aryl ketones like acetophenone and benzophenone are converted to ethylbenzene and diphenyl-methane, respectively. Friedel-Crafts acylation-silane reduction reactions can also occur in one step using these reagents thus Benzoyl Chloride reacts with benzene, triethylsilane, and BF3-OEt2 to give diphenyhnethane in 30% yield. ... 

The complexity of this reaction scheme already points out the necessary time-balance between oxidative addition, CO insertion versus deinsertion (decarbonylation), acylpalladation, carbopaUadation, and dehydropalladation events to have a selective acylpallada-tion-type reaction. This has been more recently addressed by selecting acyl chlorides that could not readily undergo dehydropalladation, hence stabilizing the organopalladium intermediates to favor their intramolecular reaction with alkenes. For instance, Pd(OAc)2 catalyzes the reaction of benzoyl chloride derivatives with enol ethers (R = OEt, Scheme 3) to give the corresponding acylpalladation products typically in 40-77% yields. " ... 

An important example of the application of these solid catalysts is represented by the comparison of the activities of HBEA and HBE A-supported In O (In Oj-BEA) (20 wt % loading) in the acylation of benzene with benzoyl chloride [34]. In Oj-BEA shows higher activity (80% benzoyl chloride conversion in 1.5 h vs. 50% benzoyl chloride convCTsion with HBEA in 3 h). This catalytic activity enhancement can be explained by considering the activation of benzoyl chloride by both protonic acid and redox sites present in In O -BEA. In fact, rare earth metal oxide species are known for their redox properties, which are expected to play a significant role in activating the benzoyl chloride according to the pathway depicted in Scheme 3.7. 

Acyl halides such as benzoyl chloride react with TMSCF3 to give a mixture of the trifluoroacetophenone and hexafluorocumyl alcohol in the presence of equimolar TBAF. Cyclic anhydrides react readily with TMSCF3 however, a stochiometric amount of TBAF is required. Acyclic anhydrides react less cleanly. ... 

The acylstannanes 874 and 875 are prepared by the reaction of acyl chlorides with (MciSnl - The symmetrical 1,2-diketones 877 can be prepared by the reaction of an excess of benzoyl chloride with (EtjSn) . Half of the benzoyl chloride is converted into the benzoyltin reagent 876, which is then coupled with the remaining benzoyl chloride under a CO atmosphere to afford the a-diketone 877[748], Triethyl phosphite is used as a ligand. 

The reaction of benzoyl chloride with (Me3Si)2 affords benzoyltrimethylsi-lane (878)[626,749,750]. Hexamethyldigermane behaves similarly. The siloxy-cyclopropane 879 forms the Pd homoenolate of a ketone and reacts with an acyl halide to form,880. The 1,4-diketone 881 is obtained by reductive elimination of 880 without undergoing elimination of /7-hydrogen[751]. 

Acyl halides are intermediates of the carbonylations of alkenes and organic-halides. Decarbonylation of acyl halides as a reversible process of the carbo-nylation is possible with Pd catalyst. The decarbonylation of aliphatic acid chlorides proceeds with Pd(0) catalyst, such as Pd on carbon or PdC, at around 200 °C[109,753]. The product is a mixture of isomeric internal alkenes. For example, when decanoyl chloride is heated with PdCF at 200 C in a distillation flask, rapid evolution of CO and HCl stops after I h, during which time a mixture of nonene isomers was distilled off in a high yield. The decarbonylation of phenylpropionyl chloride (883) affords styrene (53%). In addition, l,5-diphenyl-l-penten-3-one (884) is obtained as a byproduct (10%). formed by the insertion of styrene into the acyl chloride. Formation of the latter supports the formation of acylpalladium species as an intermediate of the decarbonylation. Decarbonylation of the benzoyl chloride 885 can be carried out in good yields at 360 with Pd on carbon as a catalyst, yielding the aryl chloride 886[754]. 

Friedel-Crafts acylation of benzene with benzoyl chloride (CgH5CCl) (j) Nitration of the product from part (1)... 

Acylation of pyridazinethiones with acetyl chloride or benzoyl chloride gives the corresponding S-acylated products. 6-Mercaptopyridazine-3(2//)-thione gives either mono- or di-S-acylated products. A bispyridazinyl derivative is formed when phosgene or thiophos-gene is used as acylating agent. 

Several triazinyl ketones isomerize to 4-acetamidopyrimidines. TTiis is seen in the C-acylation of 2,4,6-trimethyl-l,3,5-triazine (708) with benzoyl chloride in the presence of sodium amide to give the ketone (709) which undergoes a Dimroth-like rearrangement in boiling water to afford A-(2-methyl-6-phenylpyrimidin-4-yl)acetamide (710) it can be seen that the acylating agent determines the identity of the 6-substituent 64JHC145). 

Acylations were often carried out with diaziridines. Twofold acylation is normally observed when two NH groups are present. Most acylations were performed with benzoyl chloride, acetyl chloride or phenyl isocyanate (B-67MI50800). Ring opening reactions during acylation, foreseeable for intermediates of electrophilic attack on nitrogen, were observed only seldom, provided mild conditions were used. 

In their original communication on the alkylation and acylation of enamines, Stork et al. (3) had reported that the pyrrolidine enamine of cyclohexanone underwent monoacylation with acid chlorides. For example, the acylation with benzoyl chloride led to monobenzoylcyclohexanone. However, Hunig and Lendle (33) found that treatment of the morpholine enamine of cyclopentanone with 2 moles of propionyl chloride followed by acid hydrolysis gave the enol ester (56), which was proposed to have arisen from the intermediate (55). 

Acylation with aromatic acid chlorides was believed to occur on carbon 91). The dibenzoylation of the enamine (113) with benzoyl chloride in the presence of triethylamine has, however, been shown to give a mixture of three products (92). The major components are the cis and Irons isomers of the O-acylated enamino ketone (Ola and b) and the minor isomer is the 2,6-diacylated enamine (132). 

Williams and McClymont have observed that acylation reactions of the dianion of 2-(5-oxazolyl)-l,3-dithiane (15) lead to formation of 4,5-disubstituted oxazole products through a Comforth rearrangement pathway under base-induced, low-temperature conditions. For example, deprotonation of 15 with LiHMDS (3.0 equivalents) at -78°C, followed by addition of benzoyl chloride or p-chlorobenzoyl chloride and warming to 0°C, provided 16 in 74% and 47% yield, respectively. 

Similarly, the position of the acyl group in derivatives formed by the reaction with acetic hydride or benzoyl chloride and the position of the carboxymethyl group in the derivative formed by the reaction with chloracetic acid are not established. ... 

Elimination of the hydroxyaminomethyl moiety from nitro oxime 15 by treatment with a diazonium salt gave hydrazone 43 (75LA1029) (Scheme 15). The same product was obtained by coupling the diazonium salt with the compound 16. On heating in aniline, oxime 15 was transformed into Schiff base 42. Acylation of the oxime 15 with benzoyl chloride in pyridine led to a mixture of furazan 44 and dinitrile 45. 

The hydroxy group undergoes 0-acylation and deacylation (79JHC689). These reactions of functionalized hydroxyfurazans are valuable methods for modification of these compounds. Thus, hydroxybifurazan 248 was aroylated with benzoyl chloride in the presence of pyridine with concomitant cleavage of the unsubstituted furazan ring to give nitrile 262 (Scheme 170) (75LA1029). 

The reaction of 1,2,4-triazine 4-oxides 55 with water in the presence of benzoyl chloride affords 3-hydroxy-1,2,4-triazines 78. The mechanism suggested for this reaction includes acylation of the substrate at the oxygen of the iV-oxide group, followed by the addition of water to the 1,2,4-tiiazinium cation and the autoaromatization of the (T -adducts with the elimination of benzoic acid. 

Incorporation of extensive branching in the side chain similarly does not decrease pharmacologic activity. Reductive alkylation of aminoalcohol, 42, with isobutyraldehyde affords the amine, 43. Acylation of the amine with benzoyl chloride probably goes initially to the amide (44). The acid catalysis used in the reaction leads to an N to 0 acyl migration to afford iso-bucaine (45). ... 

In an analogous sequence, reductive alkylation of aminoalcohol, 46, with cyclohexanone affords the secondary amine (47). Acylation with benzoyl chloride affords hexylcaine (48) in a reaction that may again involve acyl migration. 

The oxygen atom in these molecules can in many cases be dispensed with as well substitution of sulfur for nitrogen affords a molecule whose salient biologic properties are those of a sedative and tranquilizer. Friedel-Crafts acylation of the n-butyl ether of thiophenol with benzoyl chloride gives the corresponding benzophenone. Reduction of the ketone (15) followed by... 

A somewhat different strategy is employed for preparation of the desoxy analogue containing the reversed pyrazole. Acylation of chloropyrazole with jfl-chloro-benzoyl chloride affords the ketone Reaction of that... 

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