Acyl benzoic acids

Acylation. Aromatic amines react with acids, acid chlorides, anhydrides, and esters to form amides. In general, acid chlorides give the best yield of the pure product. The reaction with acetic, propionic, butanoic, or benzoic acid can be catalyzed with phosphoms oxychloride or trichloride. 

Mocimycin has been chemically converted to aurodox by protection of the 4-hydroxy group at the pyridone moiety as the benzoylformate, followed by /V-methylation and hydrolytic removal of the protective group (1,55). Whereas aurodox esters are active growth promotors in animals, goldinamines that are A/-acylated by acids other than goldinonic acid, such as acetic, benzoic, or arylsulfonic acids, lack useful antimicrobial or growth-promoting activity (1). 

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. 

In a variation of the scheme above, alkylation of p-hydroxy-benzoic acid with cyclohexyl iodide affords the cyclohexyl ether, 55. (Under alkaline reaction conditions, the ester formed concurrently does not survive the reaction.) Acylation of the acid chloride obtained from 55 with the preformed side chain (56) gives cyclomethycaine (57). ... 

Further substitution of benzoic acid leads to a drug with antiemetic activity. Alkylation of the sodium salt of p-hydroxy-benzaldehyde (8) with 2-dimethylaminoethyl chloride affords the so-called basic ether (9). Reductive amination of the aldehyde in the presence of ammonia gives diamine, 10. Acylation of that product with 3,4,5-trimethoxybenzoyl chloride affords trimetho-benzamide (11). ... 

The benzoic acid moiety common to many of the benzamides is prepared in straightforward manner from the methyl ether of p-aminosalicylic acid 141. Acylation on nitrogen (142) followed by chlorination gives intermediate 143 benzoic acid 144 is then obtained by removal of the acetyl group. Condensation of this acid with an aminopiperidine could be achieved by means of the mixed anhydride (prepared by reaction with ethyl chlonoformate), which affords clebopride (145). Reaction with 3-aminoquinuclidine (146) of the intermediate prepared from acid 144 with carbonyldiimidazole affords zacopride (147) [36]. 

Derivatives of oxazolofS -eNl ltriazines 620 were prepared (87AJC977) by cyclodehydration of the respective 6-acylaminotriazin-5-ones 619, obtained by acylating 618, with phosphorus oxychloride or phosphorus pentoxide. 6-Phenyloxazolotriazines 620 (R1 = Ph) were also obtained directly when aminotriazinones 618 were heated with benzoic acid anhydride. By a different route, 6-aminotriazin-5-one 618 was con-... 

The aerobic reduction of aryl and alkyl carboxylates to the corresponding aldehydes. The reaction involves formation of an acyl-AMP intermediate by reaction of the carboxylic acid with ATP NADPH then reduces this to the aldehyde (Li and Rosazza 1998 He et al. 2004). The oxidoreductase from Nocardia sp. is able to accept a range of substituted benzoic acids, naphthoic acids, and a few heterocyclic carboxylic acids (Li and Rosazza 1997). 

Electron-rich aromatic compounds such as durene, p-dimethoxybenzene, mesitylene, anisole, thiophene, and fluorene can be benzoylated or acetylated by the corresponding Af-acylimidazole in trifluoroacetic acid to give the corresponding benzophenone or acetophenone derivative in good yield (Method A). As the actual acylating agent, a mixed anhydride of trifluoroacetic acid and benzoic acid has been proposed 1973... 

In a related study by the same authors, the effect of microwave irradiation on car-bodiimide-mediated esterifications on a solid support was investigated, employing benzoic acid [29]. The carboxylic acid was activated using N,N -diisopropylcarbodi-imide (DIC) through the O-acyl isourea or the symmetrical anhydride protocol (Scheme 7.9). The isourea protocol was carried out in a dichloromethane/N,N-di-methylformamide mixture in sealed vessels, whereas the anhydride reactions were carried out in l-methyl-2-pyrrolidinone (NMP) at atmospheric pressure. 

Mesitoic acid, for example, will give the amine at 0°, while benzoic acid requires a temperature of 35° for the reaction to go at a convenient rate. Presumably the higher concentration of acylium ion in the former case reacts more rapidly than a lower concentration or a less reactive source of acyl groups in the latter case.286... 

If we make the assumption that the reverse of reaction 15.5 is diffusion-controlled and assume that the activation enthalpy for the acyl radicals recombination is 8 kJ mol-1, the enthalpy of reaction 15.5 will be equal to (121 - 8) = 113 kJ mol-1. This conclusion helps us derive other useful data. Assuming that the thermal correction to 298.15 K is small and that the solvation enthalpies of the peroxide and the acyl radicals approximately cancel, we can accept that the enthalpy of reaction 15.5 in the gas phase is equal to 113 kJ mol-1 with an estimated uncertainty of, say, 15 kJ mol-1. Therefore, as the standard enthalpy of formation of gaseous PhC(0)00(0)CPh is available (-271.7 5.2 kJ mol-1 [59]), we can derive the standard enthalpy of formation of the acyl radical Af//°[PhC(0)0, g] -79 8 kJ mol-1. This value can finally be used, together with the standard enthalpy of formation of benzoic acid in the gas phase (-294.0 2.2 kJ mol-1 [59]), to obtain the O-H bond dissociation enthalpy in PhC(0)0H DH° [PhC(0)0-H] = 433 8 kJ mol-1. 

In neutral or alkaline buffer solution at 37°, the hydrolytic breakdown of A-formylbenzamide (4.166, R=H) produced only benzamide (4.167). In contrast, the higher homologues were hydrolyzed at the two amide bonds, with benzamide (4.167) and benzoic acid (4.168) formed in a 3 2 ratio. Plasma-catalyzed hydrolysis occurred predominantly at the distal amide bond to produce benzamide. Under these conditions, hydrolysis was very rapid for N-formylbenzamide (80% hydrolysis in 15 min, i. e., ca. 500-fold faster than under abiotic conditions). The rate of enzymatic hydrolysis was also markedly influenced by the length of the A-acyl group, and decreased in the order H>Me>Bu>Pr>Et. 

Carbonylation of bromobenzene (Scheme 5.7) with [Pd(TPPTS)3] required still higher temperatures (150 T). The possible acyl intermediates of such reactions [PdBr(C6H5CO) Ph3)2] and [PdBr(C6H5CO)(TPPTS)2] were synthetized and characterized [26]. Bromobenzene was also carbonylated to benzoic acid in water/toluene using a catalyst prepared from [PdCl2(COD)j and 27 in the presence of NEt3 [21]. 

From this point of view, a brief comparison of acyloxylation of cis- or irany-stilbenes in electrochemical and chemical conditions is also relevant. Oxidation of cis- or irany-stilbene at the platinum anode in the presence of acetic or benzoic acid gives predominantly meyo-diacylates of hydroxy-benzoin or, if some water is present, t/treo-monoacylate. None of the stereoisomeric erythro-mono-acylate and rac-diacylate were obtained in either case. There was no evidence of isomerization of cis- to trany-stilbene nnder the electrolytic conditions employed (Mango and Bonner 1964, Koyama et al. 1969). The sequence of reaction steps in Scheme 2.27 was proposed. Adsorption-controlled one-electron oxidation of the snbstrate takes place. Then the cis-stilbene cation-radical interact with acetate to form an oxonium ion. The phenyl groups in the oxoninm adopt the trans mntnal disposition which is thermodynamically preferential. The trany-benzoxoninm ion is the common intermediate for conversions of both cis- and trany-stilbenes and, of conrse, for all the final prodncts (Scheme... 

With phenyllithium, the iminophosphoranes of benzoic acid hydrazides 157 can be deprotonated, as shown in Scheme 62.0-Acylation of the amide-enolates 158 affords intermediates 159, which are in turn cyclized by an aza-Wittig reaction to 1,3,4-oxadiazoles 160 (68JA5626). 

Indapamide Indapamide, 4-chloro-N-(2-methyl-l-indolinyl)-3-sulfamoylbenzamide (21.3.33), is synthesized from 2-methylendoline, the nitrosation of which gives 2-methyl-1-nitrosoindoline (21.3.31). Reducing this with lithium aluminum hydride leads to formation of l-amino-2-methylendoline (21.3.32). Acylating this with 3-sulfonylamino-4-chlor-benzoic acid chloride leads to (21.3.33) [53,54]. 

The imide (86) (see (16a) in Section 4.06.5.2) is a reactive acylating reagent under mild conditions. Reaction with aniline or phenol yields diphenylurea (PhNH)2CO or diphenyl carbonate (PhO)2CO respectively. With benzoic acid, 2-phenyl-4-benzoyl-l,3,4-oxadiazoline-5-thione is formed, hence reaction of (86) with benzoic acid and nucleophiles NuH (Nu = NHPh, OPh, SPh) yields amide PhCONHPh, ester PhC02Ph, and thioester PhCOSPh respectively. With diamines R(NH2)2, (86) forms polyureas [-CONHRNH-] <89BCJ539>. 

The acylation of dibenzofuran is carried out under the usual Friedel-Crafts conditions with an acid chloride or an acid anhydride in the presence of aluminum chloride. Dibenzofuran on treatment with 2-trifluoromethane-sulfonyloxypyridine and benzoic acid in boiling trifluoroacetic acid produces the 2-benzoyl derivative in 75% yield. The species responsible for benzoyla-tion is probably a mixed anhydride of trifluoromethanesulfonic acid and benzoic acid. Dibenzofuran on treatment with 2-benzoyloxypyridine and trifluoroacetic acid also produces the 2-benzoyl compound (21%). The kinetics of the acetylation of dibenzofuran with acetyl chloride and aluminum chloride in nitroethane at 25"C have been studied. Only the 2-acetyl compound was detected by the methods used. The rate obtained is in general agreement with the studies mentioned previously. The rate of acetylation of diphenyl ether relative to toluene was 138 (+ 16), whereas that of dibenzofuran was 5.9 ( 0.3). In contrast, the benzoylation of dibenzofuran with benzoyl chloride in the presence of aluminum chloride in nitrobenzene at... 

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