P-Tetralone

Napamezole (68) is a dihydroimidazole derivative with antidepressant activity probably as a result of its combined a 2 adrenergic receptor blockuig and serotonin uptake blocking proper ties It can be synthesized by Wittig olefination of p-tetralone (65) with diethyl (cyanomethyl) phosphonate (66) and base to give nitnle 67 Imidazoline construction on the latter was smoothly... 

However, this is obviously not always the case, a counter example being the transformation of P-tetralone (23) to (S)—anunotetralin (24), with 2-amino butane serving as the amine donor. The of an (S)-selective aminotransaminase leads to a value of only... 

A number of useful reviews have appeared in the course of the last few years, and a number of chemicals, such as vitamin C, p-tetralone, hexafluoropropylene oxide, piperidine, glyoxalic acid, pinacol, p-hydroxypropiophenone, sebacic acid, p-anisaldehyde, maltol/ethyl maltol. Rose oxide, linalool, perfluorooctanoic acid, hydroquinone, etc., that are commercially made (or can be made) electrochemically have been catalogued. 

Quiroga and co-authors [101] also reported eco-friendly solvent-free approach to the synthesis of fused benzo[fjpyrazolo[3,4-b]quinolines 72 by three-component reaction of 5-aminopyrazoles, aldehydes, and p-tetralone accomplished by fusion procedure (Scheme 32). However, this method was found inapplicable for the similar reaction of a-tetralone - multicomponent procedure allowed obtaining only bispyrazolopyridines 74 instead of benzo[h]pyrazolo[3,4-b]quinolines 73. According to these experimental results, the latter were generated via preliminary synthesis of arylidentetralones 75. 

The initially-formed trienone isomerizes quantitatively to p-tetralone on treatment with catalytic amounts of trifluoroacetic acid. This acid sensitivity precludes chromatography of the crude product on normal silica gel. 

The oxidation of 1,2-dihydronaphthalene (entry 2) proceeds with a minor cleavage and yields a- and P-tetralones with a total selectivity of 93%. The greater part of the oxygen adds to the a-position. 

The reduction of alkoxynaphthalenes 398) was used by Hoechst for the synthesis of P-tetralones ... 

Scientists at Merck have reported a number of biocatalytic routes derived from screening various microorganisms targeted to produce key intermediates that are then combined with chemical reactions to prepare the target molecule. The biocatalytic step was often carried out by necessity as a result of poor chemical yield, low optical purity, or both. 6-Bromo-P-tetralone (2) was reduced to (S)-6-bromo-P-tetralol (3) by the yeast Trichosporon capitatum MY 1890 (Scheme 19.6).79 The tetralol 3 is a key intermediate for the synthesis of MK-0499 (4), a potassium channel blocker. The (S)-P-tetralol 3 was produced in gram quantities with an ee of >99% to support further development of MK-0499. Baker s yeast was tested for its ability to carry out this reduction but showed insignificant product formation. 

Review. In general, these reagents are less basic than the corresponding organo-titanium compounds. Thus they add satisfactorilv to easily enolizable ketones such as a-and p-tetralones. They can transfer even the /-butyl group to carbonyl compounds. Vi-nylzirconium compounds are sufficiently stable I > add to carbonyl groups (equation 1). 

The a- and p-tetralones are also oxidized to 2-hydroxy-1,4-naphthoquinone by KO, and a crown ether in 75% yield. In the absence of a crown ether, the oxidation proceeds slowly and in low yield (—10%). The a- and p naphthols are intermediates. ... 

Intramolecular Buchner reaction Rh(OAc)2 is more efficient than CuCl5 as the catalyst for cyclization of the a-diazo ketone 1, derived from 3-phenylpropionic acid, to bicyclo[5.3.0]decatrienone (2). This product isomerizes in the presence of triethylamine to the more stable trienone 4. A useful isomerization to p-tetralone (3) occurs in the presence of trifluoroacetic acid. 

The substitution pattern in the benzene ring of 1 controls the regioselectivity of this p-tetralone synthesis. 7-Substituted-2-tetralones are obtained from precursors substituted in the p-position (CH3, OCH3, OAc). An o-methyl substituent in 1 results in 5-methyl-2-tetralone (86%), whereas a m-methoxyl substituent in 1 results in a one-step direct conversion to 6-methoxy-2-tetralone (86%). 

Naphthols are reduced to P-tetralones (which are presumably protected from further reaction as the corresponding enolate anions) even more readily and it is surprising to find that even 6-methoxy-2-naph-thol (65) is converted into ketone (66 Scheme 11). ° Reduction of the equilenin ketal (67) was found to be highly dependent on the choice of metal. Reduction of (67 Scheme 12) or its sodium salt by lithium in the absence of an alcohol afforded (after acid hydrolysis) equilin (68) as the major product, whereas... 

Aromatization. Enamines of 6-membered cyclic ketones (cyclohexanone, a-tetra-lone, p-tetralone,...) yield arylamines on treatment with SnCU in CH2CI2 at room temperature. [SbCU is less efficient]... 

Other examples shed some light on the importance of the proton transfer in these enamine Michael additions. For example, the A 1 2 enamine of P-tetralone (Scheme 5.36c) afforded high yields of 3-substituted Al<2 enamine products, even though the A2.3 enamine isomer was not present in the reaction mixture [187] (see also ref [188]). Under the reaction conditions (toluene or ether, stirring for 3-4 days), the Al>2 isomer must isomerize to the A A isomer which reacts much faster, probably due to the greater acidity of the benzylic proton of the A2.3 isomer compared to the C3-proton of the A1-2 isomer. 

The use of enamine and imine derivatives of carbonyl substrates was also an effective means of performing aza-annulation. Treatment of either enamine 133 or imine 134 derivatives of (3-tetralone with acrylamide resulted in the formation of 135 with (85% yield)51 or without8 solvent (eq. 29). In contrast, aza-annulation of the corresponding methyl enamine of p-tetralone with methyl methacrylate generated a mixture of products.52... 

Aza-annulation of a number of dimethoxy-substituted P-tetralone derivatives, such as those represented by 136, with acrylamide was used to produce 137. In turn, 137 was an important intermediate in the synthesis of conformationally restricted congeners of dopamine (eq. 30).53... 

Homologation. The lower basicity of the anion derived from (1), compared with that of the dimethyl phosphonate, is useful for homologation of ketones containing acidic a-hydrogens, including cyclopentanone and P-tetralones. The products are ketene Jithioacetals. 

---