Diphenyl ether 4-amino

Trinitro amino diphenyl ethers, Cl2 H N407, mw 320.22, N 17.50%. The following isomer is described in the literature ... 

Another approach involves utilization of the amines for addition of a fused pyridine ring to the benzothiadiazole skeleton. The Gould-Jacobs reaction of 4-amino-2,l,3-benzothiadiazole 60 with diethyl ethoxymethylenemalonate gave the substitution product, and, after thermal cyclization in diphenyl ether, afforded the... 

The starting material may be produced by reacting 6-amino-2-methylthiopyrimidine with ethoxymethylene malonic acid diethyl ester. The intermediate thus produced is converted by boiling in diphenyl ether to 6-ethoxycarbonyl-2-methylthio-5-oxo-5,B-dihydropyrido-[2,3-d]pyrimidine. That is hydrolyzed by sodium hydroxide to cleave the ethoxy group and then ethylated with diethyl sulfate to give the starting material. 

Under flooded soil conditions, the diphenyl ether herbicides are substantially transformed into the amino derivatives, which are incorporated tightly into the soil particles. An analytical method for these amino derivatives in soil has been developed. 

The Jacobs-Gould intramolecular cyclization of diethyl N-(6-methyl-2-pyridyl)amino-methylenemalonate to 3-ethoxycarbonyl-7-methyl-l,8-naphthyrid-4-one is another reaction ideally suited to microwave heating, although conductively heated equipment was employed for laboratory-scale experiments [45]. The product is a key intermediate in the synthesis of nalidixic acid, the first of the quinolone antibacterials. The process usually is conducted at temperatures of 200-250 °C and in high dilution, with heat transfer oils such as the eutectic mixture of diphenyl ether and biphenyl. However, it proceeded rapidly, predictably and controllably under solvent-free conditions. 

When Schiff s bases (242), derived from ketones and tm-butylamine, were reacted with dimethyl methoxymethylenemalonate in diphenyl ether at 80-130°C for 1-15 hr, then at 190-250°C for 1-3 hr, 2-hydroxy-3-pyridinecarboxylates (243) were obtained by a one-pot procedure. In the first step of the reaction, the beta-carbon of the enamine moiety was involved instead of the amino group (89JHC773). 

The thermal cyclization of )V-[2-(disubstituted amino)phenyl]amino-methylenemalonates (568, R1 + H,R2 + H) by heating in boiling diphenyl ether for 5-18 min afforded quinolines (569, R1 + H, R2 =h H) in 53-81% yields [75JCS(P 1)2409]. 7V-[2-(Substituted amino)phenyl]aminomethy-lenemalonates (568, R + H, R2 = H) failed to cyclize to the corresponding quinolines (569, R1 + H, R2 = H) when heated in diphenyl ether, but their JV-(p-tosyl) derivatives (568, R2 = 4-MePhS02) gave the expected products (569, R2 = 4-MePhS02) in 72-77% yields. 

It was later claimed that the thermal cyclization of bis(aminomethylene-malonates) (601, R = H, Me, Cl, N02, R1 = Et) by heating in refluxing diphenyl ether for 15-30 min under nitrogen afforded 8-(substituted amino)quinoline-3-carboxylates (603) in 31-75% yields (78USP4123536). In the cases of the methyl and chloro derivatives (601, R = Me, Cl, R1 = Et), l,10-phenanthroline-3,8-dicarboxylates (602, R = Me, Cl, R1 = Et) could also be isolated as byproducts in 3-4% yields. 

Isomeric 6- and 8-chloro-7-fluorothiazolo[3,2-a]quinolines (768 and 769) were prepared in 29-66% yields by the thermal cyclization of [(2-sub-stituted ethyl)thio][(3-chloro-4-fluorophenyl)amino]methylenemalonates (767) in diphenyl ether at 250°C for 5 min (82EUP58392). 

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). 

The reaction of 5-amino-2-hydroxypyridine and EMME refluxing diphenyl ether for 1 hr gave 4,6-dihydroxy-1,5-naphthyridine-3-carboxylate in 20% yield after vacuum sublimation of the crude product (71JOC1331). 

The thermal ring closure of isopropylidene N-[amino(thio)carbonyl]ami-nomethylenemalonates (439, X = O, S) in boiling diphenyl ether for 5 min afforded uracil and thiouracil (1193, X = O, S) in 68% and 70% yields, respectively (84SC96I). 

Sardesai and Sunthankar studied the cyclization of diethyl )V-(2-amino-phenyl)aminomethylenemalonate (162, R = H) (57MI2 59MI1). No cyclization occurred in refluxing xylene in the presence or absence of a catalyst (p-toluenesulfonic acid or sodium hydroxide), or in acetic anhydride, or in a mixture of acetic anhydride and concentrated sulfuric acid. Benzimidazole and benzimidazolone were obtained in 20% and 66% yields, respectively, when 162 (R = H) was distilled in vacuo. Benzimidazolone was the product when 162 (R = H) was heated in boiling diphenyl ether, o-Phenylenediamine was reacted with diethyl acetylmalonate at 140°C for 4 hr to give 2-methylbenzimidazole and diethyl malonate (85S555). 

Regioselective cyclization of /V-(4-benzoyl-5-benzimidazolyl)amino-methylenemalonates (969, R = H, Me) was observed. When the cyclization was carried out in polyphosphoric acid, then 4-phenylimidazo-[4,5-/]quinoline-5-carboxylates (970) were obtained, while the thermal cyclization in diphenyl ether at 200°C, or the cyclization in a mixture of phosphoryl chloride and polyphosphoric acid afforded 4-benzoyl-8-hydroxyimidazo[5,4-g]quinoline-7-carboxylates (971) (89KFZ692). 

The nitro groups in 3,5-dinitrodiaryl ethers may be readily replaced with the residues of mono-and bis-phenols. The simplest 3,5-dinitrodiaryl ether - 3,5-dinitrodiphenyl ether - was reacted with 4-aminophenol or 4-acetamidophenol with the formation of 3-nitro-5-[4-amino(amido)]-phenoxydiphenyl ether subsequent transformation of this product led to 3-amino-5-(4-aminophenoxy)-diphenyl ether [24] (Scheme 4.9). 

Comparisons of polyimides based on different diamines obtained (Tables 5.4 and 5.5) indicate that the best solubility is typical for the polymers based on bis(3-amino-5-phenoxy)-diphenyl ethers of bis-phenols. For these polymers the lowest Tg values are also typical. 

Applications of the Conrad-Limpach reaction to the synthesis of 1-hydroxy-4,7-phenanthrolines or, more correctly, l-oxo-l,4-dihydro-4,7-phenanthrolines, from p-phenylenediamine or 6-aminoquinolines continue to be reported. l,10-Dihydroxy-3,8-dimethyl-4,7-phenanthroline has again been prepared from p-phenylenediamine,234 hot diphenyl ether being used to effect the cyclization. Other examples include the new or improved preparations of l-hydroxy-3-methyl-, 10-amino-l-hydroxy-3-methyl-,232 2-(y-chlorocrotonyl)- l,10-dihydroxy-3,8-dimethyl-, and 2,9-bis (y- chlorocrotonyl)-1,10- dihydroxy - 3,8 - dimethyl - 4,7 - phenanthro-lines.235 Compounds prepared in this way have been patented as antiasthmatic agents.178 A closely related synthesis employing poly-phosphoric acid as cyclizing agent has yielded l-hydroxy-3-phenyl-4,7-phenanthroline.236... 

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-... 

Ethyl 4-oxo-7,8,9,10-tetrahydro-4//-pyrimido[l,2-b]isoquinoline-3-carboxy-lates (196) were prepared by the cyclization of diethyl [(5,6,7,8-tetrahydro-3-isoquinolinyl)amino]methylenemalonate (195) in boiling diphenyl ether (83KGS1279 84KFZ931) and by heating in polyphosphoric acid ethyl ester (88MI5). 

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]. 

Ring transformation of the initial 6-substituted 4//-pyrido[l,2-a] pyrimidin-4-ones also occurred when 2-[(6-substituted 2-pyridyl)acrylates were heated in a high-boiling solvent. For example, heating diethyl [(4,6-dimethyl-2-pyridyl)amino]malonate in boiling diphenyl ether afforded ethyl 5,7-dimethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate... 

Compound 38 is obtained, for example, by condensing 2-amino-4-methylphe-nol with maleic acid to yield the diamide. Ring closure and the formation of the ethylene bridge occur on heating in a mixture of diphenyl ether and diphenyl at 135-155 °C in the presence of boric acid [68],... 

---