3-Tetralone methylation

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-... 

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). 

Bruce et al. carried out the cyclization of 4-phenylbutyric acid to tetralone in NaCl/AlCl3 (X(A1C13) = 0.68) at 180-200 °C [92]. The reaction between valerolactone and hydroquinone to give 3-methyl-4,7-dihydroxyindanone was also performed by Bruce, using the same ionic liquid and reaction conditions. These are shown in Scheme 5.1-60. 

The combination of CsF with Si(OMe)4 58 is an efficient catalyst for Michael additions, e.g. of tetralone 130 to methacrylamide, followed hy cyclization of the addition product to the cyclic enamide 131 in 94% yield [67]. Likewise, addition of the lactone 132 to methyl cinnamate affords, after subsequent cyclization with tri-fluoroacetic acid, the lactam 133 in 58% yield [68] whereas < -valerolactam 134, with ethyl acrylate in the presence of Si(OEt)4 59/CsF, gives 135 in 98% yield [69]. Whereas 10mol% of CsF are often sufficient, equivalent amounts of Si(OEt)4 59 seem to be necessary for preparation of 135 [69] (Scheme 3.11). 

Reaction of 1-tetralone with aryl cyanides or methyl thiocyanate, followed by aromatisation with DDQ gave good yields of benzoquinazolines. The further transformation of the methylthio product 31, via oxidation and selective sequential nucleophilic substitution of the resulting sulfones, illustrates the utility of this substituent. 2-Tetralone reacted similarly but substantial amounts of by-products were formed <06T2799>. 

N-Cyanoguanidine, 35, 69 Cyanohydrin formation, 33, 7 3-Cyano-6-isobutyl-2(l)-pyridone, 32, 34 3-Cyano-6-methyl-2(1)-pyridone, 32, 32 l-Cyano-3-a-naphthylurea, 36, 11 1-Cyano-3-phenylurea, 36, 8 Cyclic acyloins, 36, 82 Cyclization, (3-aminoethylsulfuric acid to ethylenimine, 30, 38 1,2-benzo-3,4-dihydrocarbazole from phenylhydrazine and a-tetralone,... 

The first promising asymmetric aldol reactions through phase transfer mode will be the coupling of silyl enol ethers with aldehydes utilizing chiral non-racemic quaternary ammonium fluorides,1371 a chiral version of tetra-n-butylammonium fluoride (TBAF). Various ammonium and phosphonium catalysts were tried138391 in the reaction of the silyl enol ether 41 of 2-methyl-l-tetralone with benzaldehyde, and the best result was obtained by use of the ammonium fluoride 7 (R=H, X=F) derived from cinchonine,1371 as shown in Scheme 14. 

Tetralone is readily mono- or di-alkylated at the 1-position to the exclusion of O-alky lation with a range of alkylating agents under liquiddiquid two-phase conditions without an added solvent [24], Similarly, it has been reported that anthrone undergoes mono- and di-C-alky lation at the 10-position with propargyl and allyl halides to the almost complete exclusion of O-alkylation [25]. It has been claimed that methyl-ation yields 9-methoxyanthracene [26],... 

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]. 

Reaction of 299 with benzaldehyde was found to give an equimolar mixture of diastereomeric j3-hydroxysulfoxides (314). Addition of 299 to a-tetralone 300 was more satisfactory, since the corresponding diastereomeric/3-hydroxysulfoxides 301 were formed in a 1.8 1 ratio. Their subsequent desulfuration with Raney nickel yielded levorota-tory 1-hydroxy-1-methyl-1,2,3,4-tetrahydronaphthalene 302 of unknown absolute configuration and optical purity. Similarly, addition of 299 to cyclohexene oxide leads to the formation of diastereomeric /3-hydroxysulfoxides 303 in a 2 1 ratio which, after separation, may be desulfurized to give (R,R)- and (S,S)- trans-2-methylcyclo-hexanols 304, respectively. Analysis of NMR spectra of the... 

Streptomyces griseus NRRL 8090 catalyzes a series of biotransformations of naphthalene and 2-methyl-1,4-naphthaquinone to their corresponding racemic and diastereomeric 4-hydroxy-1-tetralones (Figure 12.1). The yields of 4-hydroxy-l-tetralone obtained with S. griseus are much higher than those produced by various fungi that oxidize naphthalene. ... 

For gas chromatography analysis, samples were spiked with 2-methyl-naphthalene as an internal standard. Samples were analyzed using a Shimadzu GC-17A series gas chromatograph equipped with RTX-5 column, 15 m (length) 0.25 mm (i.d.) and 0.25 pm (film thickness). The initial column temperature was 70 °C and temperature was increased at 20 °C min 300 °C, and column temperature was held for 13 min. Retention times R naphthalene, 3.2 min 2-methyl-naphthalene, internal standard, 4.09 min 1-tetralone, 4.7 min menadione, 5.68 min 1-naphthol, 5.7 min 4-hydroxy-1-tetralone, 6.1 min and 2-methy 1-4-hydroxy-1-tetralone, 6.18,6.27,6.3 and 6.4 min. 

Tetralone from tetralone, alpha-naphthol, tetralin NaY Methyl acetate [241]... 

Fluorination of the sodium enolate of 2-methyl-1-tetralone by (-)-A-tluoro-2,10-(3,3-dichlorocamphorsultam) gives (5 )-(- -)-2-iluoro-2-methyl-1-tetralone in 70% ee, which corresponds to the opposite asymmetric induction to that achieved using non-racemic (camphorsulfonyl)oxaziridines as closely related hydroxylation reagents. ... 

The favourable effect of lithium bromide on facial enantioselective protonation of methyl tetralone enolate by a-sulfinyl alcohols has been attributed to coordination of lithium to both enolate and sulfinyl alcohol followed by competition between diastere-omeric paths involving intramolecular proton transfer the proposed transition-state model is supported by results of PM3 semiempirical calculations. ... 

As noted earlier, most classical antidepressant agents consist of propylamine derivatives of tricyclic aromatic compounds. The antidepressant molecule tametraline is thus notable in that it is built on a bicyclic nucleus that directly carries the amine substituent. Reaction of 4-phenyl-l-tetralone (18) (obtainable by Friedel-Crafts cyclization of 4,4-diphenyl butyric acid) with methyl amine in the presence of titanium chloride gives the corresponding Schiff base. Reduction by means of sodium borohydride affords the secondary amine as a mixture of cis (21) and trans (20) isomers. The latter is separated to afford the more active antidepressant of the pair, tametraline (20). 

Tetralone has been prepared by a variety of methods, but the only practical procedures are relatively recent ones involving reduction of /9-naphthyl methyl ether with sodium and alcohol2 or with sodium and liquid ammonia,3 high-pressure catalytic hydrogenation of /9-naphthol,4 or catalytic oxidation of 2-tetralol by hydrogen transfer with ethylene.6... 

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