2- Methyl-l-tetralone

Methyl-l-tetralone has been prepared from 7-phenylvaleric acid and sulfuric acid 8 and from 7-phenylvaleryl chloride and aluminum chloride.910 Its preparation from 7-valerolactone has not been described elsewhere. 

Methyl-l-tetralone, 35,96 Methyl 2-thienyl sulfide, 35, 85 Methyl 0-tiiiodipropionate, 30, 65... 

Chloro-5-methylnaphtho[l,2-c]-l,2-dithiolium chloride reacted similarly with 4-methyl-1-naphthol and with 4-methyl-l-tetralone. ... 

A soln. of 3-carbethoxy-4-methyl-l-tetralone, hydroxylamine hydrochloride, Na-acetate, and 80%-ethanol refluxed 1 hr., the resulting crude oxime (Y ca. 100%) and tosyl chloride dissolved in dry dimethoxyethane, treated with NaH-mineral oil dispersion, stirred 17 hrs. under Ng, cooled to 0°, treated with ethanolic Na-ethoxide, and stirred 2 hrs. at 0° under Ng ethyl 4-amino-l-methyl-2-naph-thoate. Y 72%. F. e. s. M. E. Garst et al., J. Org. Chem. 40, 1169 (1975). 

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. ... 

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). 

I n 1993, the first cinchona-catalyzed enantioselective Mukaiyama-type aldol reaction of benzaldehyde with the silyl enol ether 2 of 2-methyl-l -tetralone derivatives was achieved by Shioiri and coworkers by using N-benzylcinchomnium fluoride (1, 12 mol%) [2]. However, the observed ee values and diastereoselectivities were low to moderate (66-72% for erythro-3 and 13-30% ee for threo-3) (Scheme 8.1). The observed chiral inductioncan be explained by the dual activation mode ofthe catalyst, that is, the fluoride anion acts as a nucleophilic activator of the silyl enol ethers and the chiral ammonium cation activates the carbonyl group of benzaldehyde. Further investigations on the Mukaiyama-type aldol reaction with the same catalyst were tried later by the same [ 3 ] and another research group [4], but in all cases the enantioselectivities were too low for synthetic applications. 

When [l-carboxy- C]o-succinyl benzoate is administered to plants of Catalpa ovata (Bignoniaceae), it is incorporated into a-lapachones (such as 45), catalponol (46), and catalpalactone (47). Examination of the ratio in catalponol (46) after administration of [l-carboxy- C,2 - H2]o-succinylbenzoate reveals that the two protons at the 2 -posi-tion are both retained in the 3-position of catalponol (Fig. 6.9). Thus, prenylation occurs at the 2-position and does not involve an aromatic compound such as 1,4-dihydroxy-2-naphthoic acid (DHNA) (40) (Inouye and Leistner, 1988). 2-Carboxy-4-oxotetralone (COT) (43) or 2-carboxy-4-hy-droxy-l-tetralone (48) are possible acceptors for the prenyl unit. When 2-carboxy-4-hydroxy-l-tetralone (48), or its methyl ester, was introduced into the plant, the prenyl derivatives of 2-carboxy-4-oxotetralone (COT) (43) and 2-car-boxy-4-hydroxy-l-tetralone (50) were isolated as intermediates (Inouye and Leistner, 1988). 

AgF as catalysts in a 1 20 mixture of methanol and dichloromethane at low temperatures (Scheme 18.24). Table 18.3 shows examples of the protonation of silyl enolates (71) leading to the corresponding nonracemic ketones (72). Moderate asymmetric induction is observed with the silyl enolates of 2-methyl-l-tetralone and its 2-ethyl derivative (entries 1 and 2). Employment of 2,2,6-trimethylcyclohexanone-derived silyl enolate results in unexpectedly high enantioselectivity of more than 85% ee (entry 3). 2-Arylcycloalkanones are undoubtedly suitable substrates for the protonation and in fact, quite high enantiomeric excesses are obtained for the silyl enolates of 2-phenylcyclohexanone and 2-phenylcycloheptanone (entries 4-6). As for the substrates bearing a p-methoxyphenyl or 2-naphthyl group, almost perfect enantioface control has been achieved (entries 7 and 8). 

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]. 

Alkyl- or aryl-dibenzothiophenes are conveniently prepared from the 2-arylthio-cyclohexanones, which are readily cyclized and dehydrogenated to yield the respective 1-, 2-, 3- or 4-substituted dibenzothiophenes (382 equation 9 Section 3.15.2.3.2). More complex polycyclic systems are available, using suitable aryenethiols, such as naph-thalenethiols, and 2-bromo-l-tetralone to synthesize the appropriate 2-arylthio ketones. Diaryl sulfides can be converted to dibenzothiophene derivatives in satisfactory yields by photolysis in the presence of iodine (equation 10) (75S532). Several alkyldibenzothiophenes with substituents in the 2- and/or 3-positions were prepared in satisfactory yield by the condensation of dichloromethyl methyl ether with substituted allylbenzo[6]thiophenes (equation 11) (74JCS(P1)1744). 

The fixed geometry of a, 3-unsaturated ketones in the S-cis form, as observed in arylidene alkanones, influences their reactivity. For example, the reaction of arylhydrazines with 3,5-diarylidene-4-piperidones, 2-arylidene-l-tetralones, 2,6-diarylidenecyclohexanones and 2-arylideneindan-l,3-diones requires stronger conditions than for the case of their noncyclic analogues [76, 77, 78, 79, 80, 81, 82, 83, 84]. However, arylidene derivatives of cyclohexanone, 1-indanone, 4-chromanone, 4-thiochromanone and TV-methyl-4-piperidone hydrochloride react with hydrazines more easily [85,86,87,88], It is interesting to note that the more complicated and sterically hindered unsaturated ketones of the spiro type 64 react with hydrazine and phenylhydrazine very easily in the presence of piperidine, leading to pyrazoles 65 in high yields [89] (Scheme 2.16). 

An alternative cyclization via a 1-tetralone intermediate has been achieved by Inoue and May,(15) Scheme 4.5. The key intermediate (41) was prepared from frmercuric acetate gave a mixture of the three benzomorphans (42, 49% 43, 13% 44, 5%). Hydrogenation of 42 afforded 3,lla-dimethyl-8-methoxybenzomorphan (45). 

Using (2) as catalyst provided the (R) enantiomer in 99% yield, 78% ee. The key introduction of asynunetry during the synthesis of (+)-podocarp-8(14)-en-13-one was the phase-transfer-catalyzed Robinson annulation of 6-methoxy-l-methyl-2-tetralone with ethyl vinyl ketone. The authors carried out a comparative study of the A/-(4-trifluoromethyl)benzyl derivatives of cinchonine, cinchonidine, dihydrocinchonine, and dihydrocinchonidine and found that (5) produced the highest ee of the desired (S) enantiomer at —45 °C using toluene and 60% aq KOH (eq 10). ... 

CycHzation of y-arylbutyric acids. Eisenbraun et al.1 greatly prefer use of PPA to the acid chloride-AlCl3 procedure for cyclization of 4-(2,5-dimethylphenyl)-2-methyl-butyric acid (1) to 2,5,8-trimethyI-l-tetralone (2). 

Kl=acetophenone,K2=n-propyl pyruvate (CPl3C0C02-n-Pr),K3=i-butyl levulinate (CH3COCH2CH2C02- -Bu),K4=f-BuCOCH3,K5=3-MeOPhCOCH3,K6=2-py-ridyl methyl ketone, K7=l-tetralone, K8=l-acetylnaphthalene,K9=2-acetylnaphthalene,K10=ethyl levulinate,Kll=2-octanone,K12=2-phenylcyclohexanone, K13=3-pyridyl methyl ketone, K14=Me2HSiOCH2COCH3,K15=Me2HSiOCH2COPh,K16=l-cyclohexenyl methyl ketone, K17=ethyl pyruvate, K18=2,2-dimethyl-acetylacetonate,K19=methyl levulinate, K20=3,3-dimethyl-pentane-2,4-dione, K21=2-nonanone,K22=PhCOCH2Cl. 

Kl=acetophenone, K7=l-tetralone, K8=l-acetylnaphthalene, K9=2-acetylnaphthalene, K16= 1-cyclohexenyl methyl ketone, K23=4-BrPhCOCH3, K24=PhCOEt, K25= -PrCOEt,K26=EtCO-cyclopentyl... 

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