Carboxylic acids isomerization

Carboxylic acids react with butadiene as alkali metal carboxylates. A mixture of isomeric 1- and 3-acetoxyoctadienes (39 and 40) is formed by the reaction of acetic acid[13]. The reaction is very slow in acetic acid alone. It is accelerated by forming acetate by the addition of a base[40]. Addition of an equal amount of triethylamine achieved complete conversion at 80 C after 2 h. AcONa or AcOK also can be used as a base. Trimethylolpropane phosphite (TMPP) completely eliminates the formation of 1,3,7-octatriene, and the acetoxyocta-dienes 39 and 40 are obtained in 81% and 9% yields by using N.N.N M -tetramethyl-l,3-diaminobutane at 50 in a 2 h reaction. These two isomers undergo Pd-catalyzed allylic rearrangement with each other. 

Able to form Ag salt of lower solubility than AgQ in H2O. Therefore applications in photographic processes Inhibition of histidine decarboxylase activity Antifoggant for color films Anthelmintic activity Quenching for oil composition caialj si for the industrial isomerization of cis a, (3 unsaturaied carboxylic acids rubber vul-cankzate improver... 

Maleic and fiimaric acids have physical properties that differ due to the cis and trans configurations about the double bond. Aqueous dissociation constants and solubiUties of the two acids show variations attributable to geometric isomer effects. X-ray diffraction results for maleic acid (16) reveal an intramolecular hydrogen bond that accounts for both the ease of removal of the first carboxyl proton and the smaller dissociation constant for maleic acid compared to fumaric acid. Maleic acid isomerizes to fumaric acid with a derived heat of isomerization of —22.7 kJ/mol (—5.43 kcal/mol) (10). The activation energy for the conversion of maleic to fumaric acid is 66.1 kJ/mol (15.8 kcal/mol) (24). 

Some 4,5-disubstituted pyridazines exhibit ring-chain isomerism involving heterospiro compounds. For example, 5-(o-aminophenylcarbamoyl)pyridazine-4-carboxylic acid exists in a zwitterionic form in the solid state, but in a solution of DMSO it is almost exclusively 3, 4 -dihydro-3 -oxospiro[pyridazine-5(2//),2 (l //)-quinoxaline]-4-carboxylic acid (134). The equilibrium is strongly influenced by the nature of the solvent, the substituents on the pyridazine ring and the nucleophilicity of the group attached to the phenyl ring (Scheme 48) <80JCS(P2)1339). 

Although it is seldom used, esterification of pyrimidinecarboxylic acids proceeds normally. Conditions are illustrated by the conversion of pyrimidine-4-carboxylic acid (181 R = H) into its methyl ester (181 R = Me) by methanol/sulfuric acid (47%), methanol/hydrogen chloride (80%), or by diazomethane (ca. 100%) (60MI21300). The isomeric methyl pyrimidine-2-carboxylate is formed by treatment of the silver salt of the acid with methyl iodide. Higher esters, e.g. (182 R = Bu), are usually made by warming the acid (182 R = H) with the appropriate alcohol and sulfuric acid (60JOC1950). 

Orotic acid (971) has a chequered history. It was isolated in 1905 from the whey of cows milk in Italy and it was subsequently synthesized in the United States in 1907. However, the workers involved were discouraged by some difference in melting points and no direct comparison of specimens was ever made. To make matters worse, the same laboratories prepared the isomeric 5-hydroxy-2-oxo-l,2-dihydropyrimidine-4-carboxylic acid and announced it as orotic acid, again without any direct comparison. Only in 1930 did a German worker actually compare directly natural and the original synthetic orotic acid, thereby showing them to be identical (30CB1000). 

Most syntheses of this type have followed the classical Gould-Jacobs pattern (Section 2.15.5.4.2) in which 2-aminopyrazines bearing a 6-substituent give esters of 8-oxopyrido[2,3-f ]pyrazine-7-carboxylic acids (424) via the usual intermediate ethoxy-methylenemalonate adducts. In some cases the isomeric pyrazino[l,2-a]pyrimidines are formed in addition (e.g. 74CPB1864). 

Similar reactions have been observed with l,2-benzisoxazole-3-carboxylic acids (67AHC(8)277, p. 294) and the isomeric 2,l-benzisoxazole-3-carboxylic acids (67AHC(8)277, p.330). 

The reaction of methyl acetylpyruvate (312) with hydroxylamine hydrochloride gave the 3-carboxylate (313) in 76% yield together with traces of the isomeric 5-carboxylate (314) (78MIP41600). However, the sodium salt (315) of acetylpyruvic acid resulted in 3-methyl-isoxazole-5-carboxylic acid (316) as the major product. 

Because the integrity of the dihydrothiazine ring and its C-4 carboxyl substituent is crucial to useful antimicrobial activity, reactions involving this part of the cephalosporin molecule are usually undesirable. The possibilities for sulfur oxidation or alkylation, substitution at C-2 which is adjacent to both sulfur and a double bond, double bond isomerization and addition reactions, and the influence of a free carboxylic acid must all be considered in designing reactions to selectively modify other cephalosporin functionalities. 

Azetidine, 7V-bromo-, 7, 240 Azetidine, AT-r-butyl- N NMR, 7, 11 Azetidine, AT-t-butyl-3-chloro-transannular nucleophilic attack, 7, 25 Azetidine, 3-chloro-isomerization, 7, 42 Azetidine, AT-chloro-, 7, 240 dehydrohalogenation, 7, 275 Azetidine, 7V-chloro-2-methyl-inversion, 7, 7 Azetidine, 3-halo-synthesis, 7, 246 Azetidine, AT-halo-synthesis, 7, 246 Azetidine, AT-hydroxy-synthesis, 7, 271 Azetidine, 2-imino-stability, 7, 256 Azetidine, 2-methoxy-synthesis, 7, 246 Azetidine, 2-methyl-circular dichroism, 7, 239 optical rotatory dispersion, 7, 239 Azetidine, AT-nitroso-deoxygenation, 7, 241 oxidation, 7, 240 synthesis, 7, 246 Azetidine, thioacyl-ring expansion, 7, 241 Azetidine-4-carboxylic acid, 2-oxo-oxidative decarboxylation, 7, 251 Azetidine-2-carboxylic acids absolute configuration, 7, 239 azetidin-2-ones from, 7, 263 synthesis, 7, 246... 

Furan-2-carbonyl chloride, 5-alkyl-3,4-dichloro-synthesis, 4, 690 Furancarboxamides rotational isomerism, 4, 543 Furan-2-carboxylic acid, 5-acetylamino-ethyl ester reactions, 4, 647 Furan-2-carboxylic acid, amino-properties, 4, 708 Furan-2-carboxylic acid, 5-bromo-nitration, 4, 603, 711 Furan-2-carboxylic acid, 3-methyl-methyl ester bromination, 4, 604 Furan-2-carboxylic acid, 5-methyl-nitration, 4, 602... 

Homer-Emmons reagents react with trifluoromethyl ketones to form tnfluo romethylated olefins, however, the double bond can isomerize out of conjugation with the carboxylic acid group with the product olefin that bears a y-proton [37] (equation 30)... 

Peroxytnfluoroacetic acid is used tor numerous oxidations of saturated hydrocarbons and aromatic compounds It oxidizes alkanes, alkanols, and carboxylic acids with formation of hydroxylation products [29] Oxidation of cyclohexane with peroxytnfluoroacetic acid proceeds at room temperature and leads to cyclohexyl trifluoroacetate in 75% yield, 1-octanol under similar conditions gives a mixture of isomeric octanediols in 59% yield, and palmitic acid gives a mixture of hydroxypalmitic acids in 70% yield [29]... 

Phenylmethyltriazole Carboxylic Acid. —The mother substance of this compound is a triazole, viz., pyrro-n/ d-diazolc, which is one of four isomeric compounds ... 

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... 

The isomeric 4-iodopyrazole-5-carboxylic acid is cyclocondensed in a similar way. Introduction of the additional methyl group into the ring has no effect on the direction of cycloaddition 4-iodo-l,3-dimethylpyrazole-5-carboxylic acid forms only 5-lactones (Scheme 118). 

The reaction of the isomeric 3-iodo-l-methylpyrazole-4-carboxylic acid with copper phenyl- and p-amylacetylide also leads to closure of the pyranopyrazole... 

For this reason, the heterocyclization of acetylenic derivatives of pyrazolecar-boxylic acids with different arrangements in the ring of the interacting groups was studied (Table XXVI). The reaction is carried out in boiling pyridine in the presence of catalytic amounts of PhC=CCu (81IZV1342). 4-Acetylenyl-l-methylpyrazole-5-carboxylic acids (Scheme 121) are fully isomerized into the pyranopyrazoles in 20 min in 62-84% yields. 

In the heterocyclization reactions of 4-acetylenyl-l-methylpyrazole-3-carbox-ylic acids and 4-acetylenyl-l-methylpyrazole-5-carboxylic acids the behavior is the same. Isomeric l-methyl-4-phenylethynylpyrazole-3-carboxylic acid forms... 

Using a suspension of silver salts in alcohol or acetonitrile for isomerization of tolane-2-carboxylic acid leads to a change in the ratio between the resulting... 

Such an easy isomerization of acetylenylbenzoic acid amides implies the formation of a five-membered nonaromatic ring condensed with the pyrazole ring. However, the pyrazole analog of o-iodobenzamide (amide of 4-iodo-l-methylpyrazole-3-carboxylic acid) formed under heating with CuC=CPh in pyridine for 9 h only the disubstituted acetylene in 71 % yield is identical in all respects to the compound obtained from the corresponding acid by successive action of SOCI2 and NH3 (90IZV2089) (Scheme 126). 

The chemistry of fenchyl alcohol, Cj HjgO, must be regarded as in a somewhat unsettled state, as questions of isomerism arise which are as yet unsolved. It was ori nally prepared by Wallach by reducing the ketone fenchone, a natural constituent of several essential oils, by means of sodium. Later he obtained it in fairly large quantities as a byproduct in the preparation of fenchone-carboxylic acid, by passing a current of C(X through an ethereal solution of fenchone in the presence of sodium. Fenchyl alcohol has, so far, been found in one essential oil only, namely, that of the root wood of Pinus palustris. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

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