8- naphthoic acids, ring

Animals caimot synthesize the naphthoquinone ring of vitamin K, but necessary quantities are obtained by ingestion and from manufacture by intestinal flora. In plants and bacteria, the desired naphthoquinone ring is synthesized from 2-oxoglutaric acid (12) and shikimic acid (13) (71,72). Chorismic acid (14) reacts with a putative succinic semialdehyde TPP anion to form o-succinyl benzoic acid (73,74). In a second step, ortho-succmY benzoic acid is converted to the key intermediate, l,4-dihydroxy-2-naphthoic acid. Prenylation with phytyl pyrophosphate is followed by decarboxylation and methylation to complete the biosynthesis (75). 

The method described above may be used for the preparation of a wide variety of butenolides substituted in the arylidene ring with either electron-withdrawing or electron-releasing substituents. y-Lactones such as a-benzylidene-7-phenyl-A 1 -bu-tenolide are isoelectronic with azlactones, but have received much less attention. Like the azlactone ring, the butenolide ring may be opened readily by water, alcohols, or amines to form keto acids, keto esters, or keto amides.7 a,-Benzylidene-7-phenyl-A3,1 -butenolide is smoothly isomerized by aluminum chloride to 4-phenyl-2-naphthoic acid in 65-75% yield via intramolecular alkylation. 

It will be recalled that certain local anesthetic amides, such as procainamide and lidocaine, are active antiarrythmic agents. Annelation of a second aromatic ring is consistent with bioactivity. Bunaftine (21) is such an agent, prepared simply from reaction of the acid chloride of 1-naphthoic acid and... 

Groups of Class 1, when present in the 2 position, direct partly to the 1 position (in direct relation to the strength of their orienting influence), and partly to positions in the other ring, especially the 8 position, then the 6 position. Sulfonation of j3-naphthylamine gives a mixture of all four heteronuclear monosulfonic acids. The 3 position is seldom entered, and then only if the other ring bears at least one substituent. The reaction of carbon dioxide with sodium j3-naphtholate is an exception to this rule. In this case 2-hydroxy-l-naphthoic acid is formed at lower temperatures, but at higher temperatures the product is 2-hydroxy-3-naphthoic acid. 

The metal-ammonia reduction of naphthoic acids occurs initially in the ring bearing the carboxy group, the position of which is an important factor in governing the final outcome of the reduction. 

Naphthoic acids similarly undergo preferential reduction in the carboxy-bearing ring. If alcohol and limited quantities of metal (ca. 5 equiv.) are used, the 1,2,3,4-tetrahydro derivatives are formed in excellent yield. Reduction in the second ring also proceeds cleanly in the expected sense when additional metal is added, and acids (110) and (111) have been obtained in this way. ... 

The alkyl naphthalenes, such as methyl naphthalene, may be oxidized to phthalic anhydride in the same manner as naphthalene, thus making it possible to use cruder grades of naphthalene. Thus, crude naphthalene obtained by centrifuging the oils from the proper cut from the distillation of coal-tar (whizzed naphthalene) consisting principally of naphthalene to the extent of 50 to 80 per cent and usually containing considerable quantities of alkyl naphthalenes and other ring compounds may be treated in a manner similar to that used in the oxidation of pure naphthalene. The reaction products contain phthalic anhydride, benzoic acid, naphthoic acids and anhydrides, etc.81... 

The intermediate (76) for the atisine ring system was prepared from the naphthoic acid (77) by analogous transformations in an overall yield of 26%. These... 

This same asymmetric synthesis has been used to convert 3,4-dihydro-2-naphthoic acid (7) into R-(-)-8 in about 95 7o optical purity. This acid was prepared because it serves as a model for the A and B rings of anthracyclinones. 

TMLA is produced by tbe oxidation of one of the rings of the 2,6-di-methylnaphthalene molecule. 2-Formyl-6-naphthoic acid results from the incomplete oxidation of one of the methyl groups of the 2,6-dimethylna-phthalene molecule. ... 

Heptakis 6-0-t-butyldimethylsilyl-P-cyclodextrin, on reaction with 4-chloro-methyl-A -methyl-2-nitroaniline, affords the mono-3-substituted benzyl ether. P-Cyclodextrin carrying a 2-(naphthylmethyl) group at 0-6 exists with the aromatic rings within the cavity to an extent which is very temperature dependent. Temperature can therefore be used to control the degree of complexing of the aromatic system with a fluorescent naphthalene compound. Heptakis-[2,3-di-0-acetyl-6-deoxy-6-iodo]-P-cyclodextrin treated with 6-methoxycarbonyl-2-naphthol allowed access to the compound having naphthoic acid substituents at all of the primary positions, and this forms a very stable 1 1 complex with a merocyanine laser dye which is a mimic of the antenna function in photosynthesis and shows promise as a photochemical microreactor. Mono-[6-0-(8-qui-nolyl)]-P-cyclodextrin has been reported, and the stabilities of inclusion complexes with amino acid guests have been described. ... 

When bromine is used as an oxidation promoter, the bromination of the naphthalene ring occurs during the oxidation reaction and results in the formation of bromonaphthalenedicarboxylic acid. The loss of one methyl or carboxylic acid substituent during the oxidation reaction results in the formation of 2-naphthoic acid. 

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