Aryloxy carboxylations

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. 

Mirious chiral carboxylic, phosphonic. sulphonic carhamoylatctl quinine and quinidinc acids including NSAIDs, a-aryloxy carboxylic acids, acencK oumarol, A-derivatized amino acids... 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

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). 

Ethyl l-(arylimino)-l//-pyrido[l,2-c]pyrimidine-3-carboxylates exhibited anti-inflammatory activities in the carrageenan mouse paw edema model <2001JME1011>. 2-Arylimino-2,3,6,7-tetrahydro- <2000W020/058308> and 2-aryloxy-6,7-dihydro-477-pyrimido[6,l- ]isoquinolin-4-ones <2000W020/0558309> were patented as PDE inhibitors and as useful agents for treatment of respiratory disorders, respectively. 

Scheme 5 A proposed concerted mechanism for methoxide promoted methanolysis of carboxylate esters with displacement of aryloxy leaving groups.

The chemical diversity of carboxylic acid esters (R-CO-O-R ) originates in both moieties, i.e., the acyl group (R-CO-) and the alkoxy or aryloxy group (-OR7). Thus, the acyl group can be made up of aliphatic or aromatic carboxylic acids, carbamic acids, or carbonic acids, and the -OR7 moiety may be derived from an alcohol, an enol, or a phenol. When a thiol is involved, a thioester R-CO-S-R7 is formed. The model substrates to be discussed in Sect. 7.3 will, thus, be classified according to the chemical nature of the -OR7 (or -SR7) moiety, i.e., the alcohol, phenol, or thiol that is the first product to be released during the hydrolase-catalyzed reaction (see Chapt. 3). Diesters represent substrates of special interest and will be presented separately. 

The principal polyphosphazenes that have been used in hydrogels are those with linear or branched ethyleneoxy side chains, aryloxy groups with carboxylic acid substituents, or mixed-substituent polymers that bear hydrophilic methylamino side groups plus a hydrophobic cosubstituent such as phenoxy or trifluoroethoxy. Cross-linking is usually accomplished by gamma-ray irradiation or, in the case of the carboxylic acid functional species, by treatment with a di- or tri-valent cation. Here, we will consider another example based on MEEP (3.79), a polymer that is well suited to the clean method of radiation cross-linking. 

Cyclization of 2-aryloxy-3-dimethylaminopropenoates catalyzed by Lewis acids leads to a short synthesis of benzofuran-2-carboxylates (Equation 114) <2005X10061 >. 

CARBOXYLIC ESTERS TABLE 55- ALKOXY AND ARYLOXY ESTERS... 

In order to produce hetero-ring unsubstituted benzothiophenes an arylthioacetaldehyde acetal is generally employed, prepared in turn, from bromoacetaldehyde acetal and the thiophenol. An exactly parallel sequence produces 2,3-unsubstitutedbenzofurans. 2-Aryloxy-acetates (or 1-aryloxy-acetones) heated with DMFDMA, produce enamines which cycUse on treatment with zinc chloride, giving 3-unsubstituted benzofuran-2-carboxylates (3-unsubstituted 2-acetyl-benzofurans). ... 

Schoot and Klassens (1956) extended the three-point theory to further aryl- and aryloxy-alkane carboxylic acids. In their opinion, the carboxyl group of the molecule attached to the active sites reacts to form high-energy phosphate, and subsequently Sr42 reaction proceeds at the a-carbon atom. 

The glycals react with water, alcohols, phenols, carboxylic acids, and certain bases, in the presence of an acidic catalyst, in the same way as does 2,3-dihydro-4/f-pyran (which gives, for example, 2-hydroxy-, 2-alkoxy-, and 2-aryloxy-tetrahydropyrans in high yield ). (Tetrahydro-pyranyl ethers are useful for protecting alcoholic groupings during reactions in basic media, and are readily hydrolyzed with acid,) The first step of these additions would be expected to be protonation at C-2, followed by attack of the nucleophilic reagent on the resonance-stabilized, C-1 carbonium ion. 

The fact that aryl esters participate in this reaction is probably due to formation of an intermediate, [R NHCHRC02P+H(0Ar)2 + OAr], by exchange of carboxylate for aryloxy ion. 

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