Of aryl carboxylic acids

Aryl methyl ketones have been obtained [4, 5] by a modification of the cobalt-catalysed procedure for the synthesis of aryl carboxylic acids (8.3.1). The cobalt tetracarbonyl anion is converted initially by iodomethane into the methyltetra-carbonyl cobalt complex, which reacts with the haloarene (Scheme 8.13). Carboxylic acids are generally obtained as by-products of the reaction and, in several cases, it is the carboxylic acid which predominates. Unlike the carbonylation of haloarenes to produce exclusively the carboxylic acids [6, 7], the reaction does not need photoinitiation. Replacement of the iodomethane with benzyl bromide leads to aryl benzyl ketones in low yield, e.g. 1-bromonaphthalene produces the benzyl ketone (15%), together with the 1-naphthoic acid (5%), phenylacetic acid (15%), 1,2-diphenylethane (15%), dibenzyl ketone (1%), and 56% unchanged starting material [4,5]. a-Bromomethyl ketones dimerize in the presence of cobalt octacarbonyl and... 

It has been proposed that in this reaction CO2 reacts as an electrophile with [ArPd (PPh3)2] formed by reduction of the aryl-palladium(II) [102]. Aryl chlorides react too slowly with Pd° to enable an efficient carboxylation reaction. On the other hand aryl triflate and aryl bromide have similar reactivity. The synthesis of aryl carboxylic acids can then be obtained from phenols via the formation of the corresponding aryltriflate (Eq. 15) [29, 30] ... 

Table 32 Yields of 784 and 785 for the Pd(n)—Cu(ii) coupling of aryl carboxylic acids with styrene...

Reaction of Ceo with [NO][Bp4] in the presence of aryl carboxylic acids (ArC02H) in H2O yields a mixture of C6o(02CAr)x(OH)j, isomers, which were warmed with aqueous NaOH to yield the water-soluble polyhydroxylated derivatives C6o(OH) n < 20). Similar products (n < 15) have been prepared by the direct reaction of Ceo with a mixture of concentrated nitric and sulfuric acids. The polymethoxylated derivatives C6o(OMe) (n < 26) have been prepared from polychlorinated Ceo (Section 6.2.2). 

One limitation is that this re=action cannot be used for rearrangement of amides of aryl carboxylic acids because anilines are subject to further oxidation. ... 

Synthesis of aryl carboxylic acids by base catalyzed cleavage of keto pyridinium salts formed by reaction of a-haloketone derivatives with pyridine (see 1st edition). 

DMSO solution over a range of twenty pAf units (Arnett et al., 1973). Even in water, very precise values of AH-, of aryl carboxylic acids are found to correlate closely with p (Bolton et al., 1972 Matsui et al., 1974) although such a correlation does not always hold in this medium (Christensen et al., 1967). 

An easy recycling method involving both catalyst and reaction medium was achieved in a Mizoroki-Heck arylation reaction of acrylic acid, using a fluorous carbene complex (prepared in situ fl om a fluorous ionic liquid and palladium acetate) as the catalyst and a fluorous ether solvent (F-626) as the reaction medium. Because of the very low solubility of arylated carboxylic acids in F-626, the products precipitated during the course of the reaction. After separation of the products and amine salts by filtration, the filtrate, which contained the fluorous Pd catalyst, could be recycled for several runs (Scheme 13). The Mizoroki-Heck reaction was effectively promoted by a fluorous SCS pincer palladium, which is discussed in Section 3.4.5. 

Zhou, J., Wu, G., Zhang, M., lie, X., Su, W. (2012). Pd-catalyzed cross-coupUng of aryl carboxylic acids with propiophenones through a combination of decarboxylation and dehydrogenation. Chemistry-An... 

The IR spectra of ZnL Cl2(H20)2 and ZnL Cb, where n = 1 or 2, L = acetophenone acylhydrazones of a range of aryl carboxylic acids, show bidentate coordination via carbonyl O and imine N atoms." The Raman spectra of cadmium complexes with phosphorylated ligands, e.g. diisopropyl phosphoryl-guanidine (dpg), e.g. Cu(dpg)Cl2, show coordination involving phosphoryl O and guanidine N atoms. ... 

A direct formation of y-lactone 17 through benzylic oxidation of aryl carboxylic acid 16 using a hypervalent iodine(III) reagent 18 and KBr was presented by Dohi and Kita [16] (Scheme 7). This reaction was successfully applied to the synthesis of phthalides from o-alkyl benzoic acids. 

When an alkyl aryl ketone is heated with yellow ammonium polysulphide solution at an elevated temperature, an aryl substituted aliphatic acid amide is foimed the product actually isolated is the amide of the ci-aryl carboxylic acid together with a smaller amount of the corresponding ammonium salt of the oarboxylio acid. Thus acetophenone affords phenylacetamide (50 per cent.) and ammonium phenylacetate (13 per cent.) ... 

Some di-p-tolyl ketone is produced as a by-product, presumably by Interaction of the lithium salt of the carboxylic acid with the aryl lithium ... 

In the oxaziridines (1) ring positions 1, 2 and 3 are attributed to oxygen, nitrogen and carbon respectively. The latter almost always is in the oxidation state of a carbonyl compound and only in rare cases that of a carboxylic acid. Oxaziridinones are not known. The nitrogen can be substituted by aryl, alkyl, H or acyl the substituent causes large differences in chemical behavior. Fused derivatives (4), accessible from cyclic starting materials (Section 5.08.4.1), do not differ from monocyclic oxaziridines. 

Suitable starting materials for the Kolbe electrolytic synthesis are aliphatic carboxylic acids that are not branched in a-position. With aryl carboxylic acids the reaction is not successful. Many functional groups are tolerated. The generation of the desired radical species is favored by a high concentration of the carboxylate salt as well as a high current density. Product distribution is further dependend on the anodic material, platinum is often used, as well as the solvent, the temperature and the pH of the solution." ... 

By application of the Schmidt reaction, the conversion of a carboxylic acid into an amine that has one carbon atom less than the carboxylic acid, can be achieved in one step. This may be of advantage when compared to the Curtius reaction or the Hofmann rearrangement, however the reaction conditions are more drastic. With long-chain, aliphatic carboxylic acids yields are generally good, while with aryl derivatives yields are often low. 

Good yields of ketones can often be obtained by treatment of the lithium salt of a carboxylic acid with an alkyllithium reagent, followed by hydrolysis.The R group may be aryl or primary, secondary, or tertiary alkyl. Both MeLi and PhLi have been employed most often. The R group may be alkyl or aryl, though lithium acetate generally gives low yields. Tertiary alcohols are side products. 

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). 

Hydroxycarbonylation and alkoxycarbonylation of alkenes catalyzed by metal catalyst have been studied for the synthesis of acids, esters, and related derivatives. Palladium systems in particular have been popular and their use in hydroxycarbonylation and alkoxycarbonylation reactions has been reviewed.625,626 The catalysts were mainly designed for the carbonylation of alkenes in the presence of alcohols in order to prepare carboxylic esters, but they also work well for synthesizing carboxylic acids or anhydrides.137 627 They have also been used as catalysts in many other carbonyl-based processes that are of interest to industry. The hydroxycarbonylation of butadiene, the dicarboxylation of alkenes, the carbonylation of alkenes, the carbonylation of benzyl- and aryl-halide compounds, and oxidative carbonylations have been reviewed.6 8 The Pd-catalyzed hydroxycarbonylation of alkenes has attracted considerable interest in recent years as a way of obtaining carboxylic acids. In general, in acidic media, palladium salts in the presence of mono- or bidentate phosphines afford a mixture of linear and branched acids (see Scheme 9). 

With respect to the coupling reactions of stannylthiazoles with aryl halides, the union of 4-chlorobromobenzene and 2-tributylstannylthiazole constructed arylthiazole 53 [37]. The Stille reaction of 3-bromobenzylphosphonate (54) and 2-tributylstannylthiazole led to heterobiaryl phosphonate 55, which may be utilized as a substrate in a Wadsworth-Homer-Emmons reaction or a bioisosteric analog of a carboxylic acid [38], The phosphonate did not interfere with the reaction. In addition, the coupling of 5-bromo-2,2-dimethoxy-l,3-indandione (56) and 2-tributylstannylbenzothiazole resulted in adduct 57, which was then hydrolyzed to 5-(2 -benzothiazolyl)ninhydrin [39]. 

Dehydration (cf., 6, 648). A reagent (1), prepared in situ from (C6H5),PO and Tf20 in the molar ratio 2 1, effects dehydration, usually at 25°, of amides or oximes to nitriles in >90% yield. It also effects condensation of acids and amines to form amides. The reaction of an aryl carboxylic acid with an o-phenylenediamine promoted by 1 provides 2-arylbenzimidazoles in >80% yield (equation I). If the... 

For insufficiently understood reasons, there exist relatively few reports on the use of phenols and hydroxylamines as pro-moieties of active carboxylic acids. Medicinal chemists perhaps perceive these pro-moieties as potential sources of toxicity problems (see below). Furthermore, an aryl pro-moiety may unfavorably influence on solubility. 

Most data available on such prodrugs concern esters in which the phenol moiety is the pharmacologically active one (see Sect. 8.5). Here, we present some of the few studies that describe aryl esters of active carboxylic acids. 

Scheme 26 Cathodic reduction of aliphatic carboxylic acids in the presence of triphenylphosphineto aldehydes R alkyl, aryl, yields 36 -100%.

The photoactive compounds, or sensitizers, that are used in the formulation of positive photoresists, are substituted diazonaphthoquinones shown in Figure 17. The substituent, shown as R in Figure 17, is generally an aryl sulfonate. The nature of the substituent influences the solubility characteristics of the sensitizer molecule and also influences the absorption characteristics of the chromophor (79). The diazonaphthoquinone sulfonates are soluble in common organic solvents but are insoluble in aqueous base. Upon exposure to light, these substances undergo a series of reactions that culminate in the formation of an indene carboxylic acid as depicted in Figure 17. The photoproduct, unlike its precursor, is extremely soluble in aqueous base by virtue of the carboxylic acid functionality. 

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