Methoxynaphthalenes

A combination of Cp nCX —A CXC) (where = cyclopentadienyl) effectively promotes the Friedel-Crafts coupling of glycosyl fluorides with aromatic compounds, such as trimethoxyben2ene or methoxynaphthalenes. The derived C-aryl glycosides are potent antitumor agents (39). 

Methoxynaphthalene [93-04-9] M 158.2, m 73.0-73.6°, b 273°/760mm. Fractionally distd under vacuum. Crystd from absolute EtOH, aqueous EtOH, benzene or n-heptane, and dried under vacuum in an Abderhalden pistol or distd in vacuo. [Kikuchi et al. J Phys Chem 91 574 1987.]... 

The question of the occurrence of cine or aryne substitution in some of these reactions has been raised but not answered adequately. The normal product, 2-methoxynaphthalene was shown to be formed from 2-chloronaphthalene and methoxide ion, and the normal 6- and 8-piperidinoquinolines were proved to be products of piperidino-debromination of 6- and 8-bromoquinolines, all in unspecified yield. More highly activated compounds were then assumed not to react via the aryne mechanism. Even if the major product had been characterized, the occurrence of a substantial or predominant amount of aryne reaction may escape notice when strong orientation or steric effects lead to formation of the normal displacement product from the aryne. A substantial amoimt of concurrent aryne reaction may also escape detection if it yields an amount of cine-substituted material easily removed in purification or if the entire reaction mixture is not chromatographed Kauffman and Boettcher have demonstrated that activated compounds such as 4-chloropyridine do indeed react partially via the aryne mechanism (Section I,C,1). 

In a similar scheme, acylation of 2-methoxynaphthalene gives ketone, 15. This is then converted to the acetic acid by the Wilgerodt reaction. Esterification, alkylation of the carbanion (sodium hydride methyl iodide), and finally saponification affords naproxen (17). The intense current effort on nonsteroid antiinflammatory agents and acrylacetic acids in particular make... 

A first step involves the preparation of 2-Cyano-6-methoxynaphthalene (cyanonerolin). 

A number of examples of the use of molten pyridinium chloride (mp 144 °C) in chemical synthesis are known, dating back to the 1940 s. Pyridinium chloride can act both as an acid and as a nucleophilic source of chloride. These properties are exploited in the deallcylation reactions of aromatic ethers [4]. An example involving the reaction of 2-methoxynaphthalene is given in Scheme 5.1-2 [16, 18], and a mechanistic explanation in Scheme 5.1-3 [18]. 

Scheme 5.1-2 The demethylation of 2-methoxynaphthalene to 2-naphthol with pyridinium chloride.

Methoxynaphthalenes. C10H7-O.CH3, mw 158.21. There are two isomers 1-methoxy- 2-methoxy naphthalene... 

Table 12-2 gives some of Sterba s results for 1-naphthol, resorcinol, 1-methoxy-naphthalene, 3-methoxyphenol and 1,3-dimethoxybenzene. The data in the table show that the 1-naphthoxide ion is 108 times more reactive than the undissociated naphthol, which is 102 times more reactive than 1-methoxynaphthalene. The rate ratios for the monoanion of resorcinol relative to resorcinol, 3-methoxyphenol, and 1,3-dimethoxybenzene are of similar magnitudes. The dissociation of both OH groups of resorcinol gives rise to a rate constant (2.83 X 109 m -1 s-1) which, in our opinion, is probably mixing- or diffusion-controlled (see Sec. 12.9). 

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... 

Another patent apphcation (28) describes the use of zeolite/TUD-1 with optionally a metal function for a variety of reactions. In an example, as-synthesized MCM-22 / TUD-1 was tested for acylation of 2-methoxynaphthalene with acetic anhydride to 2-acetyl-6-methoxynaphthalene at 240°C. After reaction for six hours, conversion of 2-methoxynaphthalene reached 56% with 100% selectivity to 2-acetyl-6-methoxynaphthalene. Other zeolite catalysts were similarly tested, but none were nearly as effective. 

In addition to mesitylene, 2-methoxynaphthalene, 1,3,5-trimethoxybenzene, xylene, and anisole have also been benzotriazolylalkylated in this way (the latter two in lower yield). 

The reactions of the tetrahalogenobenzynes with alkoxynaphtha-lenes, in accord with the results previously mentioned, result in addition at the 1,4-positions. Thus tetrafluorobenzyne reacts with 1,2,3,4-tetra-fluoro-5-methoxynaphthalene to form (82) in good yield 90>. Reactions with 2,3-dimethoxynaphthalene lead to the formation of the adducts [83, X = F or Cl) 123>. These compounds are relatively unstable and are transformed slowly in the open atmosphere. Thus [83, X = C1) affords the di-ester (84). 

The cA-PtCl2(diphosphine)/SnCl2 constitutes the system mostly used in catalyzed hydroformylation of alkenes and many diphosphines have been tested. In the 1980s, Stille and co-workers reported on the preparation of platinum complexes with chiral diphosphines related to BPPM (82) and (83) and their activity in asymmetric hydroformylation of a variety of prochiral alkenes.312-314 Although the branched/normal ratios were low (0.5), ees in the range 70-80% were achieved in the hydroformylation of styrene and related substrates. When the hydroformylation of styrene, 2-ethenyl-6-methoxynaphthalene, and vinyl acetate with [(-)-BPPM]PtCl2-SnCl2 were carried out in the presence of triethyl orthoformate, enantiomerically pure acetals were obtained. 

SYNTHESIS OF 2-SUBSTITUTED NAPHTHALENEDIOL DERIVATIVES USING CHROMIUM CARBENE COMPLEXES 1-ACETOXY-2-BUTYL-4-METHOXYNAPHTHALENE (1-Naphthalenol, 2-butyl-4-methoxy-, acetate)... 

Friedel-Crafts acylation is widely used for the production of aromatic ketones applied as intermediates in both fine chemicals and pharmaceutical industries. The reaction is carried out by using conventional homogenous catalysts, which represents significant technical and environmental problems. The present work reports the results obtained in the Friedel-Crafts acylation of aromatic substrates (anisole and 2-methoxynaphthalene) catalyzed by Beta zeolite obtained by crystallization of silanized seeds. This material exhibits hierarchical porosity and enhanced textural properties. For the anisole acylation, the catalytic activity over the conventional Beta zeolite is slightly higher than with the modified Beta material, probably due to the relatively small size of this substrate and the weaker acidity of the last sample. However, the opposite occurred in the acylation of a bulky substrate (2-methoxynaphthalene), with the modified Beta showing a higher conversion. This result is interpreted due to the presence of a hierarchical porosity in this material, which favors the accessibility to the active sites. 

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