6- Methoxy-1-methyl-2-tetralone

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

Synthesis (Freed and Potoski (American Home), 1971 Freed, 1973 Kleemann et al., 1999,) Dezocine is prepared through the following sequence The condensation of 1-methyl-7-methoxy-2-tetralone with 1,5-di-bromopentane by means of NaH or potassium tertbutylate affords 1 -(5-bromopentyl)-1 -methyl-7-methoxy-2-tetralone this product is cyclized with NaH to give 5-methyl-3-methoxy-5,6,7,8,9,10,11,12-octahydro-5,11 -methano-benzocyclodecen-13-one i. The ketone i, by reaction with hydroxylamine hydrochloride in pyridine, is converted into its oxime ii, which is reduced with H2 over Raney Ni to a mixture of isomeric amines which were separated by crystallization of the HCI salts giving 5-a-methyl-3-methoxy-5,6,7,8,9,11 a, 12-octahydro-5,11 -methanobenzo-cyclodecen-13p-amine, which is finally cleaved with concentrated HBr. 

Methoxy-2-tetralone was methylated by the Stork method to yield 337. The latter was treated with sodium hydride and benzyl chloromethyl ether to furnish compound 338 in 60% yield. Ketalization of 338 afforded the ketal 339 which was hydrogenated with palladium on calcium carbonate to give the alcohol 340 in a yield of 92%. The alcohol 340 was oxidized with chromium trioxide in pyridine to afford the aldehyde 341 in quantitative... 

Methoxy-a-tetralone (137), which on formylation at room temperature followed by treatment with n-butanethiol in presence of p-toluenesulfonic acid gave the compound (138), which was converted with lithium dimethylcopper and acetic anhydride to (139). Subjection of (139) to dehydrogenation, hydrolysis and methylation, respectively, yielded (140) which was converted to tetralone (141) by reduction, hydrolysis and methylation of pyralidine enamine. Alkylation of (141) with 2-... 

The substitution pattern in the benzene ring of 1 controls the regioselectivity of this 3-tetralone synthesis. 7-Substituted-2-tetralones arc obtained from precursors substituted in the p-position (CH, OCH, OAc). An -methyl substituent in 1 results in 5-methyl-2-tetralone (86%), whereas a j-methoxyl substituent in 1 results in a one-step direct conversion to 6-methoxy-2-tetralone (86%). 

In Stork s synthesis (148), 5 - methyl - 6 - methoxy - 1 - tetralone (CLXXXIV) was converted into the tricyclic intermediate CLXX XVII in several steps involving condensation with dimethyl carbonate, addition of methyl isopropenylketone, and cyclization to the a, -unsaturated ketone CLXXXVI, followed by catalytic hydrogenation, replacement of the hydroxyl group in the resulting dihydro alcohol by a chlorine atom on treatment with phosphorus oxychloride in pyridine solution, and elimination of hydrogen chloride by methanolic sodium methoxide. 

In preparation for a Robinson annelation, it is often advantageous to increase the reactivity of the position adjacent to the carbonyl group by introduction of a substituent that can later be removed. Thus Turner et al." found direct condensation of 7-methoxy-l-tetralone (1) with methyl vinyl ketone or the corresponding Mannich base to show little promise. They then converted (1) into the 2-hydroxymethylene... 

Chang, H., and D. G. Morrell. 1985. Solubilities of methoxy-l-tetralone and methyl nitrobenzoate isomers and their mixture in supercritical carbon dioxide. J. Chem. Eng. Data 30 74. 

Esters, from diazoketones and organo-boranes, 53, 82 Esters, a-deuterio-, S3, 82 Esters, 7,6-unsaturated by Claisen rearrangement, 53,122 Ethers, by oxymercuration, 53, 96 Ethers, aryl methyl-, selective mono-demethylation of, 53, 93 Ethyl diazoacetate, as source of car-bethoxycarbene, 50, 94 Ethylenediamine, complexes with chromium(II) salts, 52, 62 Ethylene, with p-methoxyphenylacetyl chloride and aluminum chloride to give 6-methoxy-/3-tetralone,... 

K pulverized in xylene, which is then replaced by benzene, 5,8-di-methoxy-2-tetralone added in a N2-stream under anhydrous conditions, gently refluxed for 40 min., methyl iodide added, heated 30 min., and allowed to stand overnight —> l-methyl-5,8-dimethoxy-l,2,3,4-tetra-hydronaphthalene. Y 90%.—The insoluble K-salt of the starting material prevents double methylation. (C. A. Grob and W. Jundt, Helv. 31,1691 (1948).)... 

Suh et al.65 have reported a formal total synthesis of Mansonone F and this is described in Scheme 12. 5-Methoxy-a-tetralone (127) was converted to 1-methyl-5-hydroxy-naphthalene (128) by the standard organic reactions. Treatment of (128) with phenyl boronic acid, paraformaldehyde and propionic acid followed by catalytic hydrogenation yielded compound (129). This on alkylation gave the compound (130) which on alkaline hydrolysis was converted to acid. The acid halide underwent intramolecular Friedal-Crafts acylation affording an intermediate (131) whose transformation to Mansonone F has been accomplished by Best and Wege.59... 

Besides the aforementioned A-ring aromatic steroids and contraceptive agents, partial synthesis from steroid raw materials has also accounted for the vast majority of industrial-scale steroid synthesis. One notable exception, however, was the first industrial-scale synthesis of optically active steroids performed by workers at Roussel-UCLAF. The linear synthesis began with a suitable B—C-ring synfhon, 6-methoxy-l-tetralone (186). In a series of steps, tetralone (186) was converted to 2-methyl-2-cyanotetralone (270). Condensation of (270) with dimethyl succinate followed by carbonyl reduction, saponification, and resolution produced the optically active tricyclic acid (271). A series of reductions, a decarboxylation, and a hydrolysis produced (272). Appendage of the A-ring functionality by alkylation produced intermediate (273). Compound (273) was used as a common intermediate for the synthesis of 19-norsteroids, estrogens, and corticosteroids (230). 

Posner has devised a novel one-pot (but low yield) synthesis of ( )-9(ll)-dehydro-8-epiestrone methyl ether 210 by a coupled sequence of two Michael reactions and a Wittig reaction (tandem Michael-Michael ring closure) (Scheme 26), 6-Methoxy-l-tetralone 205 was converted, via trimethylsilyl enol ether... 

A mixture of 2-formyl-7-methoxy-l-tetralone, methyl thiotosylate, freshly fused K-acetate, and abs. ethanol refluxed 4 hrs. under Ng 2-methylthio-7-methoxy-... 

Synthesis of racemic (178) is shown in Scheme 37. Ketoester (177), synthesized from naphthalene-1,6-diol via 5-methoxy-2-tetralone, was converted into compound (180) by successive methylation at C-4, acetali-zation at C-3, reduction of the ester group to hydroxymethyl group, epoxidation of the C-5, C-6 double bond, and ring opening of the epoxide. Birch reduction of diol (180) with 18 equivalents of lithium in liquid ammonia followed by acid hydrolysis and subsequent methyl acetalization... 

An ethereal soln. of 2-bromo-2-methyl-5-methoxy>l-tetralone and BFg-etherate added drop wise at room temp, under Ng during 45 min. to an ethereal soln. of... 

Lil with stirring, which is continued until thin layer chromatography indicates completion of the reaction 2-methyl-5-methoxy-l-tetralone. Y 91%. F. e. and limitations s. J. M. Townsend and T. A. Spencer, Tetrah. Let. 1971, 137. 

---