Aryloxy acids

TABLE 48. ALKOXY AND ARYLOXY ACIDS TABLE 48 (continued)... 

The effect of 2,4-D on humans, domestic animals and wild-life has been summarised by Way (1969) and Maier-Bode (1970). This latter work also gives a summary of the literature on the toxicological and residue problems of all the important aryloxy acid derivatives. 

A number of bench-scale processes are shown in Fig. 11. Merck described the hydrogenation of an a,()-unsaturated aryloxy acid [77, 78] and of a (3-ketoester [79] as intermediate for the DPP-IV inhibitor sitagliptin MK-0431. Monsanto [80] also developed a process for naproxen (compare results in Figs. 9 and 10) and Roche [64] achieved the reduction of an a-ketoester for the Ro 40-2148 with remarkable ton of 2,000. 

The diversity of aryloxy acids which has been found to possess hypohpid-emic activity is illustrated by the following compounds ... 

Acetate Benzoate p-Nltro benzoate 3 5-Dl-nltro benzoate Aryloxy- acetlc Acid JVJV-Dl- phenyl- carba- mate iv-a- naphthyl- carba- mate p-Tolu- enesul- phonate 2 4- Dlnltro- phenyl Ether... 

Inositols, ie, hexaliydrobenzenehexols, are sugars that have received increasing study and are useful in the treatment of a wide variety of human disorders, including vascular disease, cancer, cirrhosis of the Hver, frostbite, and muscular dystrophy (269). Myoinositol esters prepared by reaction with lower fatty acid anhydrides are useful as Hver medicines and nonionic surfactants the aluminum and ammonium salts of inositol hexasulfate are useful anticancer agents (270). Tetraarjloxybenzoquinones are intermediates in the preparation of dioxazine dyes (266,271). The synthesis of hexakis(aryloxy)benzenes has also beenpubUshed (272). 

The triaLkoxy(aryloxy)boranes are typically monomeric, soluble in most organic solvents, and dissolve in water with hydrolysis to form boric acid and the corresponding alcohol and phenol. Although the rate of hydrolysis is usually very fast, it is dependent on the bulk of the alkyl or aryl substituent groups bonded to the boron atom. Secondary and tertiary alkyl esters are generally more stable than the primary alkyl esters. The boron atom in these compounds is in a trigonal coplanar state with bond hybridization. A vacantp orbital exists along the threefold axis perpendicular to the BO plane. 

Triazole-l-carboxylic acid, 4-aryloxy-, ethyl ester... 

Buu-Hoi has shown that n-alkyl methyl ketones excluding ethyl methyl ketone, yield primarily 2-monosubstituted cinchoninic acids. It has been demonstrated that the products of the condensation of isatin with aryloxyketones are the corresponding 3-aryloxy-4-quinoline carboxylic acids rather than the isomeric 2-aryloxymethylcinchoninic acids.In the case of simple a-alkoxyketones such as 1-alkoxyethyl methylketones, the preferred products are the 2-alkoxyalkylcinchoninic... 

Reaction of 9,10-difluoro-3-methyl-2,3-dihydro-7-oxo-7//-pyrido[l,2,3- /e]-l,4-benzoxazine-6-carboxylic acid (252 X = F, R = H, R = Me) with 8 M aquous solution of KOH under reflux for 6 h, and in the presence of an alcohol or phenol afforded 10-hydroxy, 10-alkoxy and 10-aryloxy derivatives, respectively (96JAP(K)96/291144, 99MI5). 

Even in Ugi reactions of chiral 4,5-dihydro-3//-pyrrole derivatives with aryloxy substituents vicinal to the cWo-cyclic imino group, a low stereoselectivity was found with either chiral or achiral isocyanides and benzoic acid leading to substituted 2-aminoearbonyl-3-aryl-oxy-1 -benzoylpyrrolid ine derivatives82. 

As already reported in Table 6, the solubility of phosphazene polymers is strongly influenced by the nature of the substituent groups attached at the phosphorus atoms along the -P=N- skeleton. Water-solubility, for instance, can be induced in polyphosphazenes by using strongly polar substituents (e.g. methylamine [84], glucosyl [495], glyceryl [496], polyoxyethylene mono-methylether [273] or sulfonic acid [497,498] derivatives), or may be promoted by acids or bases when basic (amino substituents like ethylamine [499]) or acid (e.g. aryloxy carboxylate [499] or aryloxy hydroxylate [295]) substituents are exploited. 

An important group of acylation reactions involves esters, in which case the leaving group is alkoxy or aryloxy. The self-condensation of esters is known as the Claisen condensation.216 Ethyl acetoacetate, for example, is prepared by Claisen condensation of ethyl acetate. All of the steps in the mechanism are reversible, and a full equivalent of base is needed to bring the reaction to completion. Ethyl acetoacetate is more acidic than any of the other species present and is converted to its conjugate base in the final step. The (3-ketoester product is obtained after neutralization. 

Yaodong Huang, while pursuing the synthesis of ( + )-berkelic acid (69), reported a diastereoselective cycloaddition using method H that leads to another type of 5,6-aryloxy spiroketals (Fig. 4.36).32 For example, addition of three equivalents of t-butyl magnesium bromide to alcohol 70 in the presence of the exocyclic enol ether 71 proceeds in a 72% yield to the spiroketal 72 with a 4.5 1 selectivity favoring the endo approach (Fig. 4.36). Additional experiments suggest the bromine atom decreases the HOMO-LUMO band gap and improves diastereoselectivity. 

Aryloxy-l,2-diarylethanones can be cyclodehydrated to diarylbenzofurans by heating with sodium acetate and acetic anhydride in polyphosphoric acid. Quenching the hot reaction mixture with water leads to initially violent acid-catalysed hydrolysis of the excess anhydride. 

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