Tetralones basicity

The autoxidation of cyclic ketones with dirhenium decacarbonyl under basic catalytic conditions produces dicarboxylic acids (68-73%) bicyclic ketones are converted into keto carboxylic acids and, when one ring is aromatic, quinones are obtained, e.g. 1-tetralone produces 2-hydroxy-1,4-naphthaquinone (93%), and H02C(CH2)4C0(CH2)3C02H (85%) is obtained from 1-decalone via a cyclic triketone [5]. 

The Friedlander condensation of 2,6-diaminopyridine-3,5-dicarbaldehyde (393) with various ketones has been reported (77JOC3410). Reaction of the aldehyde with acetophenone, with deoxybenzoin and with a-tetralone generates the 5,10-dihydro-l,9,10-anthyridine derivatives (394 R = H), (394 R = Ph) and (395) respectively, whilst with acenaphthenone the nonacyclic anthyridine (396) is obtained. The condensation between 2-amino-3-ethoxy-carbonyI-l,8-naphthyridine (225) and alkyl carboxylates under basic conditions produces 4-hydroxy-1,9,10-anthyridin-2-ones (397) (79BAP571). 

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]. 

Enamines derived from relatively reactive amines, such as pyrrolidine and sterically unhindered cyclic ketones, are formed rapidly either with or without acid catalysis35,42. In the case of 2-substituted cyclic ketones (2-methylcyclohexanone,l-tetralone), cyclo-heptanone and higher cyclic ketones on the one hand, and with weakly basic (e.g. morpholine) or hindered amines on the other, the use of toluene solvent and a catalytic amount of p-toluenesulphonic acid affords good yields and shortens the reaction time. 

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 effect of the basic reagent has been studied in the methylation of phenylacetone. Monomethylation proceeds better with sodium isopropoxide than with sodium ethoxide. Introduction of a second alkyl group is accomplished best with potassium t-butoxide. Sodium t-amylate allows many alkylations that fail or give poor results when carried out with sodium amide. " 1,1-Disubstituted 2-tetralones are conveniently prepared by alkylation in the presence of sodium hydride, no monosubstituted products being formed with this reagent, ... 

Aminonaphtho[l,2-b]pyrans are converted into 5,6-dihydrobenzo[h]quinolines under basic conditions through a Dimroth rearrangement. The oxygen heterocycle is formed by a Michael addition of malononitrile to a 2-arylidene-l-tetralone and the whole sequence provides an... 

Pyrans possessing substituents with an active methylene fragment in position 2 generally could be converted via their valence-bond tautomers to substituted benzenes with basic reagents [81ZC446 83AHC(34)145]. Thus, tetralone-like diketone 234 was obtained from fused 2/f-pyran 111... 

To arrive at the 2-aryl-l-tetralone, Zee-Cheng and Cheng (73JHC85, 73JHC867) used the Claisen-Schmidt aldol condensation of veratral-dehyde 30 and acetopiperone 31 to produce (3, 4 -methylenedioxy)-3,4-dimethoxychalcone 32 quantitatively (Scheme 3). On addition of hydrogen cyanide the cyanoketone 33 was formed, which after basic hydrolysis and... 

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. 

Starting material of the synthesis is 6-methoxy-l-tetralone, which is first reacted with vinylmagnesium chloride to give the corresponding vinyl alcohol. Condensation with 2-ethylcyclopentane- 1,3-dione imder basic or acidic catalysis (p-TsOH, benzene, 82 %) [54] leads, accordingtoTorgov [55], to aseco-dione, which is then reduced with Saccharomyces uvarum to the yS-hydroxy-ketone. [56]... 

The effect of ortho- and weto-substitution in the above-mentioned intramolecular Buchner reactions has been examined. When the 2-methoxy-substituted diazoketone 32 is subjected to rhodium(II) acetate catalysis, a single cycloheptatrienone 34 is obtained in 94% yield.This result is consistent with the outcome of the rhodium(II) trifluoroacetate-catalyzed intermolecular reaction of ethyl diazoacetate with anisole, which yields no product arising from addition of the ketocarbenoid on the most hindered site of the anisole. Dihydroazulenone 34 rearranges to tetralone 36 under acidic conditions, and isomerizes to the conjugated ketone 35 under basic conditions. It is interesting that the catalyzed decomposition of the para-methoxy derivative 37 provides exclusively 6-methoxy-2-tetralone 40 with no trace of the putative trienone 39. ... 

As already mentioned, Ru-tethered complexes (like 24) usually exhibited higher efficiency in ATH than the original Noyori s Ru(ll)-TsDPEN catalysts (like 26). Rhodium versions of tethered complexes were also prepared and extensively studied in TH of ketones by Wills and co-workers. They reported the use of the first tethered amino alcohol-Rh(III) catalyst 123 in ATH which, however, did not remain stable under reduction conditions (basic i-PrOH) [99]. Replacing the amino alcohol with TsDPEN linked to an arene ring resulted in complex 124 which proved to be a very effective catalyst in ATH and demonstrated improved activity over its untethered version [100]. It is noteworthy that, using the catalyst 124, a-tetralone was reduced with 99.9 % ee which was the highest enantioselectivity reported for this substrate. Even though Ru(II) catalysts are more economical and more versatile... 

This prominent name reaction looks perfect, but still has some serious drawbacks. The ylide is strongly basic, which often leads to enolization of the starting carbonyl compound. At the same time, it often suffers from a lack of nudeophi-lidty. For example, treatment of a-tetralone with methylenetriphenylphosphorane will not give any methylenated product as the substrate is deprotonated to form the enolate. Treatment of esters with an ylide often ends with recovery of the starting ester because of insuffident nudeophilicity of the ylide. These problems, however, can be overcome by the use of a gem-dimetal compound. The reaction of carbonyl compounds with gem-dimetal compounds is outlined in Scheme 5.2. 

El-Baih in 2004, has described the synthesis of naphtho[l,2-d]thiazolo[3,2-ajpyrimidine 10 (Scheme 3), by reaction of 2-arylmethylidene-l-tetralone 8 with thiourea under basic conditions to give naphtho[l,2-d]pyrimidine 9 which then cyclized with chloroacetic acid to afford the target compound 10 [21]. 

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