3.4- Dihydro-2-naphthoic acid

DIMETHOXY-3,4-DIHYDRO-2-NAPHTHOIC ACID (2-Naphthoic acid, 3,4-dihydro-6,7-dimethoxy-)... 

In a similar manner, 3,4-dihydro-2-naphthoic acid, m.p. 111-114° (corr.), and 7-methoxy-3,4-dihydro-2-naphthoic acid, m.p. 149-150.5° (corr.), have been obtained in 35% yields. 

Dimethoxy-3,4-dihydro-2-naphthoic acid can be dehydrogenated to give 6,7-dimethoxy-2-naphthoic acid. The yield of the latter was 85% after distillation and crystallization from alcohol. 

This method of preparation is essentially that used by Robinson and Crowley for the preparation of 6-methoxy-3,4-dihydro-2-naphthoic acid. They first used concentrated sulfuric acid but found that this reagent caused sulfonation. 

In a procedure for the synthesis of 6,7-dimethoxy-3,4-dihydro-2-naphthoic acid (IV) by the method of G. P. Crowley and R. Robinson, ethyl y-veratrylbutyrate (I) is formylated with ethyl formate by dropwise addition of a solution of 1 and ethyl formate in ether to a suspension of sodium ethoxide in ether at —10°. After acidification, the formyl derivative II is collected by ether extraction and cyclized to III with a mixture of 90% phosphoric acid and concentrated sulfuric acid at 0-10°. Saponification gives the acid IV, m.p. 193°. 

A solution of 3-hydroxymethyl-l-phenyl-3,4-dihydro-2-naphthoic acid lactone (1.2 g, 4.6 mmol) in THF (30 mL) was added dropwise to a slurry of UAIH4 (0.8 g, 21 mmol) in THF (30 mL). The mixture became warm and developed a red-brown color, which disappeared within 30 min. The mixture was refluxed for 3 h, cooled, and treated first with EtjO/EtOAc (1 1 v/v) and then with H O. The organic layer plus ether extracts of the aqueous phase were dried (Na2S04) and evaporated to give a liquid, which crystallized from EtjO/petroleum ether (bp 30-60°C) to give prisms yield 0.8 g (70%) mp 97-98°C. 

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. 

A soln. of 1-phenyl-3-hydroxymethyl-3,4-dihydro-2-naphthoic acid lactone in tetrahydrofuran added slowly to a stirred slurry of LiAlH4 in the same solvent, and refluxed 3 hrs. 2-hydroxymethyl-7b-phenyl-la,2,3,7b-tetrahydro-lH-cyclo-propa[a]naphthalene. Y 70%. F. e. s. L. H. Klemm et al., J. Org. Chem. 37, 2043 (1972). 

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