Ethers, 4-nitrophenyl synthesis

Outline a reasonable synthesis of 4 nitrophenyl phenyl ether from chlorobenzene and phenol... 

Nifedipin Nifedipine, dimethyl ether l,4-dihydro-2,6-dimethyl-4-(2 -nitrophenyl)-3,5-piridindicarboxylic acid (19.3.16), is synthesized by a Hantsch synthesis from two molecules of a j3-dicarbonyl compound—methyl acetoacetate, using as the aldehyde component—2-nitrobenzaldehyde and ammonia. The sequence of the intermediate stages of synthesis has not been completely established [20-23]. 

Synthesis of[ 1-11C]-labelled ethyl, propyl, butyl and isobutyl iodides, and N-[1-11 C-ethyl]lidocaine, 178, N-[1-11C-butyl]bupivacaine, 179, and 3-nitrophenyl [1-11C]propyl ether, 180... 

Aromatic and aliphatic amino ethers have been synthesized by this method. An example of the formation of a cyano ether is the preparation of p-cyano benzyl methyl ether from the substituted benzyl bromide and sodium methoxide (84%). Also, certain aryloxyacetonitriles, AtOCHjCN, are made by the condensation of chloroacetonitrile with sodium phenoxides in a solution of methyl ethyl ketone containing a small amount of sodium iodide (70-80%). Aromatic nitro ethers, like o- and p-nitrodiphenyl ether, have been prepared by the Ullmann procedure (84%). The synthesis of alkyl p-nitrophenyl ethers has also been accomplished with good yields (55-92%). ... 

An alternate procedure was used by Shafer et al. (1966) in their synthesis of p-nitrophenyl diazoacetate. The key to this synthesis was the use of a chloroformate intermediate. To a 16-fold excess of diazomethane in ether (10 ml) was added dropwise a solution of 48.4 mg of p-nitrophenyl chloroformate. After the solution stood overnight at 4°C, the excess diazomethane was removed under a stream of N2 and the ether evaporated under reduced pressure. The residual yellow oil was dissolved in 2 ml of benzene and chromatographed on an alumina column using benzene as the eluant. The first fraction contained 48 mg of product which could be recrystallized from chloroform-hexane (m.p. 92-94°C). These authors reported that several other diazoacetates can be prepared by this procedure. 

A. Synthesis of Substrates. -Nitrophenyl acetate (PNPA) was synthesized from -nitrophenol and acetic anhydride according to the general method of Bender and Nakamura (11). The ester was recrystallized four times from petroleum ether giving a melting point of 78-79 C (lit. 81-82 C). 

A third route, the fluorination of nitrophenyl esters of perfluoro-alkylene ether dicarboxylic acids, has now been developed for synthesis of highly stable aryl perfluoroalkylene ether intermediates of the type shown by III. 

A recent synthesis of armepavine is of special interest because of the means by which the phenolic hydroxyl was introduced. p-Nitrophenyl-acetyl chloride was condensed with 3,4-dimethoxyphenethylamine and the resulting amide cyclized in the usual way by treatment with phosphorus oxychloride in chloroform. The methiodide of the generated dihydroiso-quinoline on reduction yielded the amino compound LXXXVII, which was diazotized and boiled with dilute sulfuric acid. The DL-armepavine thus obtained (m.p. 166°) yielded an 0-methyl ether (m.p. 92°), which on Hofmann degradation gave rise to a methine (m.p. 87°) and a vinylstilbene (m.p. 79°). Their properties were the same as those of the compounds obtained from the natural base (111a). 

The simplest example of a functional micelle is (49), previously demonstrated to be more effective than its trimethylammonium analogue in both esterolysis and bimolecular elimination reactions. It has now been demonstrated that micelles of (49) are more effective catalysts for the hydrolysis of p-nitrobenzoyl phosphate dianion at high pH than non-functional surfactants. " 2,4-Dinitrochloro- and fluoro-benzene react with micelles of (49) at high pH 10" times faster than with hydroxide ion at a comparable external pH. The initial product is (50) and this in turn is hydrolysed in micelles 2.6 x 10 times faster than is 2,4-dinitrophenyl 2-(trimethylammonium)ethyl ether in water at pH 12. Acyl transfer between p-nitrophenyl acetate and (49) gives an intermediate whose hydrolysis is not micelle catalysed. In contrast to the rate acceleration observed in that case, hydrolysis of p-nitrophenyl acetate is inhibited by micelles of (51) since the phenoxide nucleophile is weak and at the reaction pH its micelles are zwitterionic, not cationic. Synthesis of functional choline-type micelles is facilitated by the use of sulphonate (52), which is reactive towards thiophenoxide in aqueous micelles, but its water-insoluble trifluoromethanesulphonate reacts with a range of anions under phase-transfer conditions. " ... 

The successful synthesis of these compounds showed the feasibility of using the carbodiimidazole coupling reaction in the formation of aryl-azido ATP analogs. For the general synthesis of the arylazidocarboxylic acids, 4-fluoro-3-nitroaniline is first diazotized in a concentrated hydrochloric acid medium in the presence of sodium nitrite [Eq. (2)]. The diazonium salt is subsequently treated with sodium azide, which results in the formation of a light-sensitive 4-fluoro-3-nitrophenyl azide (IV) [Eq. (3) ]. The structure of (IV) has been confirmed by its melting point of 52°-52.5° (recrystallized from petroleum ether) its NMR spectrum, 7.47 ppm (2 protons), 7.78 ppm (1 proton) and its mass spectrum, m/e 182. 

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