Methoxy-diphenyl ether

Sinkkonen S, Rantalainen A-L, Paasivirta J, Lahtipera M (2004) Polybrominated Methoxy Diphenyl Ethers (MeO-PBDEs) in Fish and Guillemot of Baltic, Atlantic and Arctic Environments. Chemosphere 56 767... 

The second compound important for the structural determination of chaenorhine (171) was obtained from A A -dimethylchaenorhine by Hofmann degradation. The resulting Hofmann base 174 was hydrogenated catalytically to the tetrahydro compound 177. Next, it was hydrolyzed in the presence of base and the product esterified with diazomethane. 6-Methoxy-diphenyl ether (3,4 -/ ,/ -dipropionic acid dimethyl ester) (178), which could be identified by comparison with a synthetic product, was obtained in a yield of 40% (see Scheme 32). 

Berbamine occurs in B. vulgaris, B. aquifolium (12, 13), B. thunbergii (22), Stephania cepharantha Hayata (23), and in B. swaseyi Buckley Mahonia swaseyi Fedde) to the extent of about 2 % in the dried roots (24). Santos (21) found that berbamine was isomeric with oxyacanthine and that oxidation of berbamine methyl ether produced 4, 5-dicarboxy-2-methoxy-diphenyl ether (VIII, R = CH3), as in the case of oxyacanthine. The constitution of the isoquinoline portion of the molecule was determined by von Bruchhausen, Oberembt, and Feldhaus (18). The products obtained after a Hofmann degradation of 0-methylberbamine followed by ozonization were the same two dialdehydes, XXXV and 4, 5-diformyl-2-methoxydiphenyl ether (XXXIV), as were obtained from 0-methyloxy-acanthine by similar treatment. On the basis of these facts von Bruchhausen and coworkers concluded that berbamine and oxyacanthine are structural isomers. If o.xyacanthine is assigned the formula XXVI then berbamine must have the formula XXXI or vice versa. 

Preparation by reaction of p-chlo-robenzoyl chloride with 3-methoxy-diphenyl ether in chloro-benzene in the presence of aluminium chloride first at r.t., then for 4 h at 90-95° [839]. 

Yields of 54% of 2-methoxy-4 -methyl diphenyl ether from -bromotoluene and guaiacol, and 60% of 2-mcthoxy-5-methyl-diphenyl ether from 3-bromo-4-methoxytoluene and phenol, have been obtained by the same method in the laboratory of the submitters,... 

The thermal cyclization of [(3-chloro-4-fluorophenyl)amino][4-methoxy-phenyl)methylthio]methylenemalonate (789, R = Cl, R1 = 4-MeOC6H4) in diphenyl ether at 250°C for 3 min gave 2-substituted quinoline-3-carbox-ylate (790, R = Cl, R = 4-MeOC6H4) in 66% yield (82EUP58392). 

The thermal cyclization of (methoxymethylthio)(3,4-difluorophenyl-amino)methylenemalonate (789, R = F, R1 = MeOCH2) by heating in diphenyl ether at 240°C for 5-10 min yielded 6,7-difluoro-2-(methoxy-methy thio)quinoIine-3-carboxyIate (790, R = F, R1 = MeOCH2 (87BRP2190376). 

Haglund PS, Zook DR, Buser H-R, et al. 1997. Identification and quantification of polybrominated ethers and methoxy-polybrominated diphenyl ethers in Baltic biota. Environ Sci Technol 31 3281-3287. Hagmar L, Bergman A. 2001. Human exposure to BFRs in Europe. BFR 107-111. 

A few extensions of the Conrad-Limpach synthesis have been applied to the synthesis of 4,7-phenanthrolines. Unlike o-phenylenediamine, which gives a quinoxaline derivative, p-phenylenediamine reacts with excess of ethyl ethoxalylpropionate to give an intermediate bisanil, which cyclizes in hot diphenyl ether to afford 3,8-dicarboethoxy-l,10-dihydroxy-2,9-dimethyl-4,7-phenanthroline in high yield.237 With diethyl ethoxymethylenemalonate as condensing agent, 6-amino-8-methoxy-quinoline has been converted into 2-carboethoxy-l-hydroxy-6-methoxy-4,7-phenanthroline.238 A related condensation affording 1-... 

Heating diethyl (l-isoquinolylamino)methylenemalonates in diphenyl ether gave ethyl 4-oxo-4//-pyrimido[2,l-a]isoquinoline-3-carboxylates (97) (78USP4127720). Cyclization of diethyl[(4-amino-l-isoquinolyl)amino] methylenemalonate in a mixture of acetic anhydride and pyridine in methylene chloride at ambient temperature afforded ethyl 7-acetylamino-4-oxo-4//-pyrimido[2,l-a]isoquinoline-3-carboxylate [84JAP(K)84/172472]. The 7-nitro derivative was prepared similarly. Cyclization of diethyl [(7-methoxy-3-methyl-l-isoquinolyl)amino]methylenemalonate in polyphos-phoric acid at 130°C for 6 h gave 10-methoxy-6-methyl-4//-pyrimido[2,l-a]isoquinolin-4-one in 29% yield [94IJC(B)795]. 

Photochemical cyclization reactions of iodinated diphenyl ethers to produce dibenzofuran derivatives have also been studied545. l,3-Diiodo-2-(4 -methoxyphenoxy)-5-nitrobenzene affords 4-iodo-8-methoxy-2-nitrodibenzofuran upon irradiation in acetone. 

The starting substances for the synthesis of the required diphenyl ethers are suitably substituted o-nitrochlorobenzenes, which react with phenols containing in the ortho position a methoxy, nitro, or halogen group. 

The same condensation-cyclization sequence with 4-methoxy-phenylhydrazine (292), however, proceeded in only 17% yield (113), so an alternative synthesis was devised for the important 8-oxygenated derivatives, such as 293 and 294, which employed a more conventional Fischer indole reaction (Scheme 47) (113). In the event, condensation of keto ketal 295 with hydrazine 280 gave hydrazone 296. Cyclization in hot diphenyl ether gave ketone 297, which, upon dehydrogenation, protection of the phenol as the benzoate, and chlorination gave 298. Deprotection and/or methylation afforded the target chloro-y-carbolines (299-301). 

A synthesis of magnoline has not yet been achieved but an attempt toward this end led to the related compound XXV (15). Reaction of the acid chloride of 2-methoxy-4, 5-bis(carboxymethyl)diphenyl ether (XVII) with 3-methoxy-4-benzyloxyphenethylamine afforded the... 

The structure of the diphenyl ether moiety of 0-methylthalicberine was determined by degradation. 0-Methylthalicberine dimethochloride was converted through the Hofmann elimination reaction to a methine base (CVII) which was oxidized with permanganate to an acid identified as 2-methoxy-5,4 -dicarboxydiphenyl ether (XVIII) (81). 

Heating a 3-(2-hydroxyphenyl)propionate ester in diphenyl ether with palladium-charcoal induces a combined cyclization and dehydrogenation [3437], Simultaneous de-O-benzylation and cyclization of a 2-(benzyloxy)acrylic acid by heating with acetyl chloride containing phenyltrimethylammonium iodide gives good yields of a fused pyran-2-one [3836]. In contrast, an o-methoxy-benzylidenemalonic acid (as its potassium salt) cyclizes in the cold when treated with trifluoroacetic acid-trifluoroacetic anhydride [3938]. 

Tetra- and penta-bromodiphenyl ethers and their methoxy derivatives have been detected in herring, salmon, seals, and commercial fish oils from the Baltic [140] in the tens to hundreds of ng/g lipid range, with levels increasing up the food chain. The samples also contained polychlorinated diphenyl ethers ranging from hexa- to decachloro and methoxy derivatives of octa- and nonachloro diphenyl ethers. 

XXXVII). Further reduction (Clemmensen) yielded 3,4,4 -trimethoxy-6,6 -diethyl-l,l -dimethyl-2,3 -diphenyl ether (XXXVIII), which proved to be identical with a synthetic product obtained by the Ullmann condensation of 1,2-dimethoxy-4-ethyl-5-methyl-6-bromobenzene and the sodium salt of 2-methoxy-4-ethyl-5-methylphenol. Oxyacanthine therefore is composed of two benzyltetrahydroisoquinoline rings linked by two oxygen bridges and must have the formula XXVI or XXXI. 

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