Aromatic carboxylic acids, synthesis

Hofmann s amine synthesis can be applied to both aliphatic and aromatic carboxylic acid amides, benzamide, C HsCONH, thus giving aniline, C4H5NH,. 

Phenolic esters (1) of aliphatic and aromatic carboxylic acids, when treated with a Lewis acid as catalyst, do undergo a rearrangement reaction to yield ortho- and para-acylphenols 2 and 4 respectively. This Fries rearrangement reaction is an important method for the synthesis of hydroxyaryl ketones. 

Although the ability of microwaves (MW) to heat water and other polar materials has been known for half a century or more, it was not until 1986 that two groups of researchers independently reported the application of MW heating to organic synthesis. Gedye et al. [1] found that several organic reactions in polar solvents could be performed rapidly and conveniently in closed Teflon vessels in a domestic MW oven. These reactions included the hydrolysis of amides and esters to carboxylic acids, esterification of carboxylic acids with alcohols, oxidation of alkyl benzenes to aromatic carboxylic acids and the conversion of alkyl halides to ethers. 

In a more recent study using dedicated multimode microwave reactors for chemical synthesis, which enable temperature and power control, it was demonstrated that microwave irradiation could be effectively employed to couple aromatic carboxylic acids to polystyrene Wang resin [25], if the symmetrical anhydride procedure was used, and not the three-component O-acylisourea activation method [19]. Almost quantitative loading was achieved in l-methyl-2-pyrrolidone (NMP) at 200 °C within 10 min under... 

Kwakman et al. [65] described the synthesis of a new dansyl derivative for carboxylic acids. The label, N- (bromoacetyl)-A -[5-(dimethylamino)naphthalene-l-sulfonyl]-piperazine, reacted with both aliphatic and aromatic carboxylic acids in less than 30 min. Excess reagent was converted to a relatively polar compound and subsequently separated from the derivatives on a silica cartridge. A separation of carboxylic acid enantiomers was performed after labeling with either of three chiral labels and the applicability of the method was demonstrated by determinations of racemic ibuprofen in rat plasma and human urine [66], Other examples of labels used to derivatize carboxylic acids are 3-aminoperylene [67], various coumarin compounds [68], 9-anthracenemethanol [69], 6,7-dimethoxy-l-methyl-2(lH)-quinoxalinone-3-propionylcarboxylic acid hydrazide (quinoxalinone) [70], and a quinolizinocoumarin derivative termed Lumarin 4 [71],... 

A powerful and efficient method for the preparation of poly(ketone)s is the direct polycondensation of dicarboxylic acids with aromatic compounds or of aromatic carboxylic acids using phosphorus pentoxide/methanesulfonic acid (PPMA)16 or polyphosphoric acid (PPA)17 as the condensing agent and solvent. By applying both of these reagents to the synthesis of hexafluoroisopropylidene-unit-containing aromatic poly(ketone)s, various types of poly(ketone)s such as poly(ether ketone) (11), poly(ketone) (12), poly(sulfide ketone) (13), and poly-... 

In addition to the synthesis of saccharin, also a number of other side-chain oxidations have been studied leading to aromatic carboxylic acids by indirect electrochemical oxidation using chromic acid as oxidizing agent. They include the oxidation of p-nitrotoluene 2,4-dinitrotoluene toluene, p-xylene, and p-tolualdehyde... 

Formation of Aromatic Carboxylic Acids The Kolbe-Schmitt Synthesis... 

The synthesis of 2-methylbutanoic acid (Expt 5.129) is illustrative of the method. Other organometallic reagents undergo a similar carboxylation reaction, and examples of the use of organolithium and organosodium reagents are included in the section on the synthesis of aromatic carboxylic acids (Section 6.13.3, p. 1069). 

The hydrolysis of nitriles under either acidic or basic conditions, which has already been discussed in Section 5.11.2, p. 671, for alkyl and aralkyl nitriles, is equally applicable to the synthesis of aromatic carboxylic acids (Expt 6.153). The aromatic nitriles are readily obtained by the Sandmeyer reaction (see Section 6.7.1, p. 923). 

The structural interrelationships of these aromatic carboxylic acid derivatives and the retrosynthetic analyses that indicate the broad methods of synthesis are similar to the aliphatic analogues. The methods of preparation described in these sections are those which appear to work best in the aromatic field. 

Some aromatic carboxylic acids are also commercially important. Benzoic acid is used as an ingredient in medications, a preservative in foods, and a starting material for synthesis. Benzoic acid can be produced by the oxidation of toluene with potassium permanganate, nitric acid, or other strong oxidants. 

Lane CF, Myatt HL, Daniels J, Hopps HB (1974) Organic synthesis using borane-methyl sulfide II Reduction of aromatic carboxylic acids in the presence of tnmethyl borate J Org Chem 39 3052-3054... 

Cesium phenolates were introduced by Kellogg [16] for the synthesis of crown compounds, after crown ether diesters had been obtained in good yields from the cesium salts of aromatic carboxylic acids and oligoethylene glycol dihalides... 

Microwave irradiation of a mixture of an acid anhydride, an amine adsorbed on silica gel, and TaCl5/Si02 is a solvent-free method for the synthesis of A-alkyl and A-aryl-imides [47]. Ni(II) promotes the conversion of an acrylamide to ethyl acrylate via a Diels-Alder adduct with (2-pyridyl)anthracene [48], Aromatic carboxylic acids [49] and mandelic acid [50] are efficiently esterified with Fc2(S04)3 XH2O as catalyst. Co(II) perchlorate in MeOH catalyzes the methanolysis of acetyl imidazole and acetyl pyrazole [51]. Hiyama et al. used FeCb as a catalyst for the acylation of a silylated cyanohydrin. The resulting ester was then cyclized to 4-amino-2(5H)-furanones (Sch. 5) [52]. 

Alane (AIH3) and its derivatives have also been utilized in the reduction of carboxylic acids to primary alcohols. It rapidly reduces aldehydes, ketones, acid chlorides, lactones, esters, carboxylic acids and salts, tertiary amides, nitriles and epoxides. In contrast, nitro compounds and alkenes are slow to react. AIH3 is particularly useful for the chemoselective reduction of carboxylic acids containing halogen or nitro substituents, to produce the corresponding primary alcohols. DIBAL-H reduces aliphatic or aromatic carboxylic acids to produce either aldehydes (-75 °C) or primary alcohols (25 C) Aminoalu-minum hydrides are less reactive reagents and are superior for aldehyde synthesis. ... 

There has been considerable research into the electrolytic reduction of aromatic carboxylic acids to the corresponding aldehydes. A general procedure has been described in which key elements are the use of the ammonium salt of the acid, careful control of the pH and the presence of an organic phase (benzene) to extract the aldehyde and thus minimize overreduction. The method appears to work best for relatively acidic substrates for example, salicylaldehyde was obtained in 80% yield. Danish workers have shown that, under acidic conditions, controlled electrolytic reductions are possible for certain pyridine-, imidazole- and thiazole-carboxylic acids. In these cases, it is thought that the product aldehydes are protected by geminal diol formation. A chemical method which is closely related to electrolysis is the use of sodium amalgam as reductant. Although not widely used, it was successfully employed in the synthesis of a fluorinated salicylaldehyde. ... 

Schultz, A. G., Malachowski, W. P., Pan, Y. Asymmetric Total Synthesis of (+)-Apovincamine and a Formal Synthesis of (+)-Vincamine. Demonstration of a Practical "Asymmetric Linkage" between Aromatic Carboxylic Acids and Chiral Acyclic Substrates. J. Org. Chem. 1997, 62, 1223-1229. 

Sinha, J., Layek, S., Mandal, G. C., Bhattacharjee, M. A green Hunsdiecker reaction synthesis of P-bromostyrenes from the reaction of a,p-unsaturated aromatic carboxylic acids with KBr and H2O2 catalyzed by Na2Mo04.2H20 in aqueous medium. Chem. Common. 2001, 1916-1917. 

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