Phenyl 2-pyridyl ether

Friedel-Crafts cyclization benzo[i]thiophenes from, 4, 873 Ethanol, 2-(4-imidazolyl)-synthesis, 5, 484 Ethanol, (S)-l-phenyl-synthesis, 1, 434 Ethanol, 2-phenyl-isochroman synthesis from, 3, 788 Ether, allyl pyridyl... 

According to U.S. Patent 2,676,964 to 1.0 mol of potassium amide in 3 liters of liquid ammonia, is added 1.0 mol of 2-benzylpyridine. After 15 minutes, 1.1 mols of 3reaction product decomposed with water and ether extracted. The ether layer is dried over Sodium sulfate and after evaporation the residue is distilled, giving the 3-phenyl-3-(2-pyridyl)-N,N-dimethylpropylamine, BP 139°-142°C/1-2 mm. The maleate is produced by reaction with maleic acid. 

It has been found that the combination of Lewis acids and surfactants is particularly effective for catalyzing Diels-Alder reactions in water. The effect of micelles of SDS, CTAB, dodecyl heptaoxyethy-lene ether (Q2E7), and copper and zinc didodecyl sulfate [M(DSb] on the Diels-Alder reaction of 3-(p-substituted phenyl)- l-(2-pyridyl)-2-propen-l-ones (Figure 12.1) with cyclopentadiene was studied. 

Both glycosyl phenyl sulfones and glycosyl 2-pyridyl sulfones have been employed as donors in glycosylation reactions. The phenyl sulfones are activated with MgBr2 etherate in THF at room temperature (Schemes 4.54 and 4.55) [307,309], Considerable rate enhancement has been reported either by heating at reflux or by the use of ultrasonication. 

Whitlock, G.A., Fish, P.V, Fray, M.J., Stobie, A. and Wakenhut, F. (2008) Pyridyl-phenyl ether monoamine reuptake inhibitors Impact of lipophilicity on dual SNRI pharmacology and off-target promiscuity. Bioorganic and Medicinal Chemistry Letters, 18, 2896—2899. 

Methyl 2-pyridylacetate in ether with MP yields a mixture of 106, 107, and 108 which could be formed through a zwitterion corresponding to 95,296 and 109. The 1-propanoyl derivative of 109 is obtained from l-(2-pyridyl)butan-2-one. However, ethyl 2-pyridylacetate with phenyl-propiolic esters apparently gave only 110, and, if sodium methoxide was... 

A mixture of the crude oil of methyl 2-bromo-3- 4-[2-(5-ethyl-2-pyridyl)ethoxy]phenyl propionate (73.0 g) thiourea (14.2 g), sodium acetate (15.3 g) and ethanol (500 ml) was stirred for 3 hours under reflux. The reaction mixture was concentrated under reduced pressure, and the concentrate was neutralized with a saturated aqueous solution of sodium hydrogencarbonate, to which were added water (200 ml) and ether (100 ml). The whole mixture was stirred for 10 min to yield 5- 4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl -2-imino-4-thiazolidinone as crystals (0.3 g, 523.0%). Recrystallization from methanol gave colorless prisms, melting point 187°-188°C, dec. 

Cone, sulfuric acid (11 ml) was added to 4-(N,N-dimethylamino)-2-phenyl-2-(2-pyridyl)-valeronitrile (6.3 g) at 0°C. Then water (1 ml) was added thereto. After being heated at 90°C for 3 hours, the mixture was poured into ice-water, adjusted to pH 10 with 10% aqueous sodium hydroxide and extracted with ethyl acetate (3x50ml). The extracts were combined, and washed with water, dried over magnesium sulfate and evaporated under reduced pressure. The obtained crude crystal was recrystallized from diethyl ether to give 4-(N,N-dimethylamino)-2-phenyl-2-(2-pyridyl)-valeramide (1.89 g). MP 132-134°C. 

Stability of the compounds 86 varies dramatically with the nitrogen substituent. Methyl and phenyl derivatives (86 R = Me or Ph) are moderately stable crystalline solids—often hydrated (87 or 88 X = OH). The 2,4-dinitrophenyl derivative [86 R = CeH3(N02)2, R = H] is less stable but can be isolated as orange prisms (mp 112°C) It readily rearranges to the diaryl ether 96 (mp 128°C) with which it was originally confused.The monomeric 5-nitro-2-pyridyl derivative is similarly unstable and in solution dimerizes giving adduct The 4,6-di-... 

The generality of the rearrangement is further illustrated by the reaction of 2,2 -furil with hydroxide ion in dry ether (Table 1). Likewise, 2,2 -pyridil is rearranged in hot methanol solution (40 min) to give the sodium salt of 2,2 -pyridilic acid (86%). Acidification, however, affords bis(2-pyridyl)methanol by decarboxylation since 2,2 -pyridilic acid (16) is structurally similar to a -keto acid. Benzilic rearrangement of 2,2 -pyridil with methanolic nickel(ll) and cobalt(II) acetates results in the formation of metal complexes of 2,2 -pyridilic acid (17 92%). A plausible mechanism is summarized in Scheme 4. Rearrangement is also observed with 2,2 -quinaldil, but benzil, 2,2 -furil or 1-phenyl-2-(2 -pyridyl)ethane-1,2-dione are not susceptible to these metal template reactions. 

Figure 26. A force-field (CHARMm) optimized structure of porphyrin 20 with the peptide gly-gly-phe. Hydrogens are omitted for clarity except those of peptide NH3. The phenyl group of phe is not far from vdW contacts to the pyrrole (dav = 3.95 A) the -NH3 protons have distances from 1.90 to 2.05 A to the crown ether oxygen the carboxylate group comes close to neighboring pyridyl protons with dav = 3.0 A. ...

In the pyridine series it is not necessary to activate the ether linkage by a nitro group if an amine hydrochloride is used instead of the free base. Jerchel and Jakob1104 obtained a number of iV-substituted 4-pyridinamines in good yield from 4-pyridyl phenyl ethers and amine hydrochlorides. 

The prototype of the aminoalkyl ethers is diphenhydramine, a benzhydryl ether which more than a half-century after its introduction remains still widely used for allergic conditions. Structural analogues with various ring substituents (Me, OMe, Cl, and Br) in one of the aromatic rings also have been developed, as have compounds with a 2-pyridyl group replacing one of the phenyl groups (Table 37.3). 

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