1.2.3.4- Tetrahydro-2-naphthoic acid

Naphthoic acid was reduced with sodium in liquid ammonia to 1,4-dihydro-1-naphthoic acid which, after heating on a steam bath with 20% sodium hydroxide for 30 minutes, isomerized to 3,4-dihydro-l-naphthoic acid (yield 63%) [399]. 2-Naphthoic acid treated with 4 equivalents of lithium in liquid ammonia and ethanol gave 69% yield of 1,2,3,4-tetrahydro-2-naphthoic acid. With 7 equivalents of lithium, l,2,3,4,5,8-hexahydro-2-naphthoic acid was obtained in 82% yield [986]. 

Tetrahydro2oline [84-22-0] 2-(l,2,3,4-tetrahydro-l-naphthyl)2-imida2olin, (Tysine, Visine) (40), a sympathomimetic and nasal decongestant, is made by the condensation of 1,2,3,4-tetrahydro-l-naphthoic acid or its methyl ester with 1,2-ethylenediamine. 

Lateral metallation is the key step in the synthesis of the pen-fused isocoumarin 69 from 5,6,7,8-tetrahydro-1 -naphthoic acid <00S 1113>. 

A methoxyaldehyde, m.p. 52-53°, of unassigned structure is reported in the patent literature [6] as the product from the reaction of 2-methoxy-5,6,7,8-tetrahydronaphthalene with N-methylformanilide and phosphorus oxychloride. This reaction in our hands gave a 50% yield of methoxyaldehyde (VII), m.p. 51 6-52°, whioh was oxidized with potassium permanganate in acetone solution to 3-methoxy-5,6,7,8-tetrahydro-2-naphthoic acid. The structure of the latter was established by mixture m.p. with an authentic sample prepared [7] by converting 3-hydroxy-5,6,7,8-tetrahydro-2-naphthoic acid to the... 

Fischer esterification of 5,6,7,8-tetrahydro-l-naphthoic acid, prepared from 5,6,7,8-tetrahydro- 1-naphthylamine via a recently published method [9], produced the methyl ester, which was distilled twice, b.p. 158-5-159° at 15-5 mm (spectral sample), wff 1-5437 lit. [14] values b.p. 93-5-96-5° at 0-5-1-0 mm, f 1-5431. 

Melhoxy-5,6,7,8-tdrahydro-2-naphthoic acid—To 0 45 g (0 0024 mole) of the methoxyaldehyde in 25 ml of acetone 0 24 g of magnesium sulphate in 26 ml of water was added. Potassium permanganate (0 62 g) in 22 ml of water was introduced dropwise at 50° over 1 hour. The filtered mixture was acidified to give 0 32 g (65%) of tan powder, m.p. 108-112°. Recrystallization from aqueous methanol afforded white crystals, m.p. 116-117° no depression in m.p. was observed on mixing with authentic methoxyacid prepared [7] from 3-hydroxy-5,6,7,8-tetrahydro-2-naphthoic acid via the methyl ester of the methoxyacid. 

As a key feature of the TASP approach, the template is designed to direct and reinforce the folding of the covalently attached secondary structure elements in the predetermined tertiary structures (Scheme 1), e.g. a four a-helical bundle. The major purpose of artificial turn-inducing mimics is to constrain, when incorporated at the appropriate location, the peptide chain into a semi-rigid, defined, spatial arrangement. 39 8-(Aminomethyl)-5,6,7,8-tetrahydro-2-naphthoic acid (Amhn) is designed to substitute for the central dipeptide unit of a reverse turn and is prepared in a five-step procedure starting from commercially available 4-phen-ylbutanoic acid 40 (Scheme 3). 

Esterification of 8-oxo-5,6,7,8-tetrahydro-2-naphthoic acid (285 g, 1.5 mol) was achieved by refluxing its soln in MeOH (2.8 L) containing coned H2S04 (50 g). After 8h, the solvent was removed and afforded crude, partially solid, dark-colored ester, which was decolorized in CH2Cl2/hexane on charcoal and further purified by crystallization and liquid chromatography of the mother liquor (Merck 60 silica gel, CH2Cl2/hexane 1 1) yield 280.7 g (92%) mp 76-77°C. 

Beams and Manders reported (177) the synthesis of the tricyclic dione 349 via two different synthetic routes. The Australian chemists utilized an approach analogous to one developed earlier by Masamune (178) during the synthesis of atisine and kaurene. They prepared tetrahydro-7-methoxy-2-naphthoic acid (350) from 7-methoxytetral-l-one by published procedures. 

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. ... 

Synthesis of an Atisine-type Intermediate.—Two synthetic routes to the tricyclic dione (50) were explored by Beames and Mander.30 Using an approach analogous to one developed by Masamune,31 they converted l,2,3,4-tetrahydro-7-hydroxy-2-naphthoic acid (51) into the bromide (52). The reaction of the latter with t-butoxide produced a 3 1 mixture of the dienone ethers (54) and (55). The use of deblocking and oxidation reactions furnished the diketone (50). Reduction of (50) with borohydride furnished a 2 3 mixture of the alcohols (56) and (57). 

A mixture of 540 grams (9.0 mols) of ethylenediamine, 270 grams (1.53 mois) of 1,2,3,4-tetrahydro-aipha-naphthoic acid, and 360 mi (4.32 mois) of concentrated hydrochloric acid was introduced into a two-liter, three-necked flask fitted with a thermometer, stirrer, and distillation takeoff. The mixture was distilled under a pressure of about 20 mm of mercury absolute until the temperature rose to 210°C. Thereafter, heating was continued under atmospheric pressure and when the temperature reached about 260°C, an exothermic reaction was initiated. The heat was then adjusted to maintain a reaction temperature of 275° to 280°C for 45 minutes and the mixture thereafter cooled to room temperature. 

Na added in small pieces with Dry Ice-acetones cooling under Ng to a suspension of 20.2 g. 5,6,7,8-tetrahydro-2-methoxy-l-naphthoic acid in liq. NHg-abs. ether until a blue color persists, then methyl iodide added during 10 min. 18.9 g. crude l,4,5,6,7,8-hexahydro-2-methoxy-l-methylnaphthoic acid. - No hydroxylic proton donor is required. F. e. s. M. D. Bachi et al., J. Org. Chem. 34, 126 (1969). 

Tetrahydro-6-hydroxy-2-naphthoic acid. 2-Hydroxytetralin-6-carboxylic acid... 

Moreover D-configuration could also be determined for the auxins (-l-)- -allyl-phenylacetic acid, (—)-indane carboxylic acid and (-)-i,2,3,4-tetrahydro-i-naphthoic acid (LVIII, LIX, LX). 

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). 

Side chains may be degraded, as in the example already cited in which 5,6,7,8-tetrahydro-2-naphthoic acid appears as a by-product in the reaction of ethyl 6-tetralyl ketone with morpholine and sulfur. Ammonimn polysulfide and long-chain alkyl phenyl ketones give some benzoic acid. Ethyl 9-anthryl ketone, on the other hand, produces anthracene in 85% yield, possibly owing to the great lability of a substituent in the 9-position of anthracene. 

Naphthalene, 21, 34, 44, 45 2-acetamido-, 60 dihydro-, 45 tetrahydro-, 45 Naphthoic acid, 51 a-Naphthol, 8, 44 /3-Naphthol, 8, 44 Naphthol, 6-acetamido-2-, 60 2-amino-1-, 60 Naphthoresorcinol, 5-8, 29 Naphthylamines, 60 Neomenthol, 73 Nicotinic acid, 63... 

A mixture of 2-(3,5-dimethoxybenzyl) succinic acid and acetic anhydride refluxed 20 min., excess acetic anhydride removed under reduced pressure, poly-phosphoric acid added to the residue, and heated 2 hrs. with stirring on a steam hath 4-oxo-5,7-dimethoxy-l,2,3,4-tetrahydro-2-naphthoic acid. Y 73.5%. Z. Horii, T. Katagi, and Y. Tamura, Ghem. Pharm. Bull. 11, 309 (1963) ring closure s. a. R. Quelet, R. Dran, and G. Lukacs, G. r. 258, 2590 (1964). 

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