6- Methoxy-1-tetralone

A more recent synthesis for (14-9) takes quite a different course. The first step comprises the displacement of one of the halogens in 1,4-dibromobenzene by the alkoxide from A-2-hydroxyethylpyrrolidine (15-2) in the presence of 18-crown ether to afford (15-3). Condensation of the lithium salt from (15-3) with 6-methoxy-tetralone (15-4) followed by dehydration of the initially formed carbinol give the intermediate (15-5), which incorporates the important basic ether. Reaction of that compound with pridinium bromide perbromide leads to the displacement of the vinylic proton by halogen and the formation of bromide (15-6). Condensation of that product with phenylboronic acid in the presence of a tetrakistriphenyl-phosphine palladium catalyst leads to the coupling of the phenyl group by the formal displacement of bromine. The product (14-9) is then taken on to lasoxifene (14-11) as above [16]. 

Ziegler and Wang have achieved a synthesis of ( )-estrone from 6-methoxy-tetralone based on Cope rearrangement and polyene cyclization methodology (Scheme 28). ... 

Aboraia AS, Makowski B, Bahja A, Prosser D, Braneale A, Jones G, Simons C (2010) Synthesis and CYP24A1 inhibitory activity of (E)-2-(2-substituted benzylidene)- and 2-(2-substituted benzyl)-6-methoxy-tetralones. Eur J Med Chem 45 4427 434... 

B. Heterocyclic - A number of ring-aza steroids are conveniently prepared by total synthesis. The 6,7-diaza steroid was prepared from a bicyclic enamine intermediate with m-methoxydiazonium fluoroborate which was used to introduc the adjacent nitrogens prior to completion of the rest of the steroidal skeleton. The enamines of g-tetrolone and 6-methoxy -tetralone were treated with a-bromoacetate and then treated with hydrazine hydrate followed by either malonyl dichloride or propiolactone to give 13,14-diozo steroids. By this sequence the D-homo-diaza steroidal system could also be prepared.The 8,13-diazaestranes were prepared by... 

Pbenylhydiazon der S-Methoxy-tetralon.(l)-suUc>na iiie-(3 oder 4) 15 I1144. 

The same product can be obtained by the analogous treatment of the diketone (363) here three reactions take place successively cyclization, demethylation, and isomerization. This combination of reactions represents a method for synthesizing D-homoequilenin (21) from the methoxy-tetralone (8) in three stages with an over-all yield of 28% [141, 458]. 

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). 

In the first of these sequences, often called the Torgov-Smith synthesis, the initial step consists in condensation of a 2-alkyl-cyclopentane-l,3-dione with the allyl alcohol obtained from 6-methoxy-l-tetralone and vinylmagnesium chloride. Although this reaction at first sight resembles a classic SN displacement, the reaction is actually carried out with only a trace of base. 

Rh2(OAc)4-catalyzed decomposition of m-methoxy-substituted diazoketones 244 furnishes 6-methoxy-2-tetralones rather than the expected bicyclo[5.3.0]decatrienones. This demonstrates that the direction of ring opening in the norcaradienone intermediate 245 may well be influenced by the nature and position of a substituent. 

The facile nitration of a wide variety of ketones with TNM in Table 2 is illustrative of the synthetic utility of enol silyl ethers in facilitating a-substitution of carbonyl derivatives. It is necessary to emphasize here that the development of a strong charge-transfer (orange to red) coloration immediately upon the mixing of various ESEs with TNM invariably precedes the actual production of a-nitroketones in the thermal nitration (in the dark). The increasing conversion based on the time/yields listed in Table 2 qualitatively follows a trend in which electron-rich ESE from 6-methoxy-a-tetralone reacts faster than the relatively electron-poor ESE from cyclohexanone. 

The stereospecific C-alkylation of a range of benzylic ketones, such as tetralones, 2-phenylcyclohexanones and cycloheptanones, and 2-phenyl-y-lactones, has also been described [8]. For example, Af-(4-trifiuoromethylbenzyl)cinchonidinium bromide catalyses the reaction of 1,5-dibromopentane with 7-methoxy-l-methyl-2-tetralone to yield the (R)-l-(5-bromopentyl) derivative (75% yield with 60% ee). 

The Robinson annulation reaction of 7-methoxy-l-methyl-2-tetralone with methyl vinyl ketone in the presence of A,-(4-trifluoromethylbenzyl)cinchonidinium bromide produces the S-isomer of the tricyclic compound (Scheme 12.10) with an 81% conversion (81% ee) [8]. 

The preparation of 6-methoxy-2-naphthol is of particular interest as the starting point in many synthetic sequences. It is readily converted to 6-methoxy-2-tetralone through a Birch reduction... 

Methoxy-l-tetralone will be available from K K Laboratories, New York, although the submitters have used a material, m.p. 77-80°, produced by Osaka Yuki Gosei K. K., Nishinomiya-shi, Japan. 

Crystals of 6-methoxy-l-tetralone may separate from the solution on cooling, but redissolve upon addition of the cooled diethylaluminum cyanide solution. 

Allenylacetylenes, 50,101 ir-Allylnickel bromide, 52,199 Aluminum amalgam, 52, 7S Aluminum chloride, with ethylene and p-methoxyphenylacetyl chloride to give 6-methoxy-(3-tetralone, 51, 109... 

Ethylenediamine, complexes with chro-mium(ll) salts, 52,62 Ethyl diazoacetate, as source of car-bethoxycarbene, 50,94 Ethylene, with p-methoxyphenylacetyl chloride and aluminum chloride to give 6-methoxy-d-tetralone, 51,... 

Phe residue, obtained as a pale yellow oil, weighs approximately 7.4 g. and consists of l-cyano-l-hydroxy-6-methoxytetra-lin and a small amount of unchanged 6-methoxy-l-tetralone. Phe oil is transferred to a lO-rnl. Glai.sen flask, a small... 

The cyanohydrin initially formed is unstable and readily reconverted to the starting 6-methoxy-l-tetralone on evaporation of the extracts unless slight acidity of the solution is maintained by addition of a trace amount of p-toluenesulfonic acid monohydrate. As this acid is relatively insoluble in methylene chloride, it should be added directly to the flask used for evaporation of the solvent. 

The present method developed by the submitters is the only practical process for preparation of l-cyano-6-methoxy-3,4-dihydronaphthalene. Birch and Robinson have reported that 6-methoxy-l-tetralone did not react with hydrogen cyanide or sodium acetylide. 

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