Oxidation 1-methoxynaphthalene

Identical kinetics are exhibited in the analogous oxidations of 1- and 2-methoxynaphthalene to 4-methoxyl-l-naphthyl acetate and 2-methoxy-1,4-naphthoquinone respectively . In these cases the radical-cations may react with acetate ion thus... 

In addition to products 8—11, varying amounts of N-formylanilines 12) are formed when methoxynaphthalenes are oxidized. Yields for Ar=3-Cl-C6H4 are given along with those for Ar = 1-naphthyl (in parentheses). 

Asymmetric Hydroformylation of Vinylarenes a-Arylpropanals, the products of asymmetric hydroformylation of vinylarenes, serve as useful intermediates for pharmaceutical drugs. For example, (5)-2-arylpropanals can be oxidized to the corresponding (5)-2-arylpropanoic acids, such as (5)-ibuprofen (Ar = 4-isobutylphe-nyl), (5)-naproxen (Ar = 6-methoxynaphthalen-2-yl), and (5)-suprofen (Ar = 4-(2-thienylcarbonyl)phenyl) (see later in chapter. Scheme 4.4). Styrene is thus one of the most popular substrates used to test new catalyst systems. Representative ligands and their use as Pt or Rh complexes in the asymmetric hydroformylation are summarized in Figure 4.1 and Table 4.1. (See also Scheme 4.3.)... 

Anodic nuclear substitution by methoxide or cyanide ions gives acceptable yields only for methoxybenzenes and methoxynaphthalenes. The nucleophile is attached to the point of highest positive charge density in the radical-cation and for many examples this leads to ipio-substitution. Oxidation of 1,4-dimethoxybenzene in methanol containing potassium hydroxide leads to the quinone diketal 8 [69]. The reaction is a general one for 1,4-dimethoxybenzenes [70, 71] and 1,4-... 

Synthesis of racemic naproxene Friedel-Crafts acylation (aluminum chloride - nitrobenzene) of p-naphthol methyl ether affords 2-acetyl-6-methoxy naphthalene, which, when treated with either dimethyl sulfonium or dimethylsulfoxonium methylide, gives 2-(6-methoxynaphthalen-2-yl)propylene oxide. Treatment of the latter with boron trifluoride etherate in tetrahydrofuran gives 2-(6-methoxynaphthalen-2-yl)propionaldehyde, which is oxidized using Jones reagent (4 M chromic acid) to yield the racemic 2-(6-methoxynaphthalen-2-yl)propionic acid. 

Enzyme assays were performed in 1.5 mL microcentrifuge tubes containing 165 /nL of incubation buffer (0.25 M Tris-HCl, 0.1 mM EDTA, pH 7.4), 50 fiL of 10 mM glutathione in incubation buffer, and 25 /nL of appropriately diluted enzyme. The reaction was initiated by addition of 10 /nL of benzo [a]pyrene-4,5-oxide in acetonitrile (0.875 mg/mL). The assay was stopped by addition of 0.25 mL of acetonitrile containing 300 /nM 2-methoxynaphthalene as an internal standard. The solution was kept overnight in the dark at 4°C, and then 500 /nL of distilled water was added. The mixture was centrifuged before analysis by HPLC. Production of both the glutathione and diol derivatives was linear with time and protein up to 15 minutes and 500 /ng/mL, respectively. 

Arnold reported that the photoaddition of methanol and trifluoroethanol to 1,1-diphenylethene occurs in the photoreaction using methoxynaphthalenes as an electron donating sensitizer [35, 113]. The proposed mechanism for this reaction is shown in Scheme 34. The radical anion of the alkene is first produced by photoinduced electron transfer from the electron donating sensitizer to the alkene and it is protonated in a Markownikoff fashion to form the 1,1-diphenylethyl radical. The resulting radical is then oxidized by the radical cation of the electron donating sensitizer to generate the cation of the alkene. Finally, a nucleophilic attack of alcohol on this cation affords the alkoxylated product. 

The highiy oxygenated antifungai/anticancer naturai product ( )-diepoxin o was prepared in the laboratory of P. Wipf. The coupling of the two substituted naphthalene rings was achieved via the Ullmann condensation of a phenolic compound with 1-iodo-8-methoxynaphthalene. The aryl iodide coupling partner was used in excess and the condensation was conducted in refluxing pyridine in the presence of a full equivalent of copper(l)-oxide. 

Among the metal acetates which have been studied recently, Co(III) acetate engages in electron transfer more easily than Pb(IV), Mn(III), and Ce(IV) acetates (Heiba et al., 1968a, 1969a, b Heiba and Dessau, 1971). Kinetics have shown, both with Mn(III) and Co(III) acetates, that electron transfer is fast and reversible and is followed by a rate-determining step whose nature depends on the aromatic. Oxidation of 1-methoxynaphthalene in acetic acid at 100°, for example, leads to l-acetoxy-4-methoxynaphthalene [eqns... 

Friedel-Crafts acylation of 2-methoxynaphthalene (nerolin) is followed by a WUlgerodt-Kindler oxidation of the methyl ketone. After esterification, the methyl group is introduced by alkylation, and the enantiomers are finally separated by co-crystaUisation with cinchonidine. 

Nickel catalysis has also been used in the formation of biaryls, such as (51), by substitution of the methoxy group in 1-methoxynaphthalene by tolylmagnesium bromide. It is also reported that the reaction of aryl or heteroaryl tosylates with phenylmag-nesium bromide to give biaryl derivatives is catalysed by palladium complexed with heteroatom-substituted secondary phosphine oxide ligands. 

A novel regiospecific synthesis of islandicin was described by Glein etal. 145) (Scheme 21). Thus Fries rearrangement of l-propionyloxy-5-methoxynaphthalene followed by methylation and bromination yielded the ketone (172). Alkylation with sodium diethyl malonate followed by demethylation, ester hydrolysis and decarboxylation gave the acid (173). Elbs oxidation and sulfuric acid cyclisation of the acid yielded 1-O-methyl-islandicin (174). 

The reaction of chlorophosphine oxides with metal acetylides is typically tolerant of bulky groups on the alkyne (Scheme 4.354) [529]. A recent example of this entails the synthesis of an alkynylphosphine oxide from chlorodiphenylphosphine oxide and l-ethynyl-2-methoxynaphthalene. Treatment of the alkyne with BuLi and subsequent addition of the... 

A final synthetic effort in the yohimbine alkaloid area concerns the studies reported by Loewenthal and his coworkers (Scheme 3.92) (143). The aim was to develop an efficient method to prepare the bicyclic enone 21, which serves as a key intermediate in the Woodward reserpine synthesis strategy (19). The route for preparation of 21 began with Friedel Crafts reaction of 2-methoxynaphthalene (523) with the oxalyl chloride equivalent 524, a process which afforded the acenaphthenoquinone 525. Oxidative-decarboxylation of 525 yielded the naphthalene-carboxylic acid 526 which was transformed by Birch reduction and esterification to the dihydro-derivative 527. Carboxyla-tion then provided geminal diester 528 which was epoxidized. Sequential lactonization and methylation afforded tricyclic lactone 529. Ester cleavage with subsequent decarboxylation gave lactone 530 which was demethylated to provide 531. While no further effort was given to the development of this... 

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